Day 2 :
Keynote Forum
James Michaelson
Harvard University, USA
Keynote: The role of micro CT in the imaging of surgical pathology specimens
Time : 09:00-09:25
Biography:
James Michaelson is the Director of the Laboratory of Quantitative Medicine, Member of the Departments of Pathology and Surgery at the Massachusetts General Hospital and Associate Professor in Harvard University. His research concerns: The assembly of very large databases on patients; the development of improved mathematical methods for predicting cancer outcome; the analysis of patient outcome and cost; the analysis of cancer screening; the mathematics of growth; the mathematics of metastasis; the use of modern computer speech and telephony to design systems that improve patient compliance and the development of advanced method for imaging cancer specimens.
Abstract:
The absence of real-time, detailed, 3D, information on the composition surgical specimens presents an enormous challenge in surgical oncology and pathology. The problem is especially pressing for breast cancer where as many as nearly 1 in 3 patients undergoing lumpectomy have been found, upon pathological examination of the slides to be margin positive. These patients need to return to the hospital for re-excision, sometimes multiple times in order to achieve negative margins. A solution may be found in a relatively new technology, Micro CT, a high resolution X-ray imaging method that has been widely used in industry and materials science but little used in medicine. Over the past three years we have imaged a great variety of surgical specimens with three Micro CT machines (SkyScan 1173 Micro CT, Xradia MicroXCT-200 and Nikon Metrology XTH225). Our findings indicate the Micro CT is able to provide 3D images of surgical specimens which can identify within 10 minutes, most of those breast cancer patients later found to be margin positive on pathological analysis as well as to identify a small number of patients whose cancers appear to be margin positive on Micro CT alone. Micro CT can also identify lymph nodes in cancer specimens including nodes not detected by pathological dissection. These findings suggest that Micro CT has a considerable potential for providing the surgeon and pathologist with rapid, accurate, actionable information on the status of the surgical specimen while the patient is still in the OR.
Keynote Forum
Haodong Xu
University of California at Los Angeles, USA
Keynote: Immunohistochemical Detection of EGFR Mutations and ALK Rearrangement in Lung Adenocarcinoma
Time : 09:25-09:50
Biography:
Haodong Xu received his MD, MS, and PhD from Suzhou Medical College. He subsequently completed a residency in Anatomic and Clinical Pathology at Barnes-Jewish Hospital/Washington University School of Medicine, and a fellowship at the Armed Forces Institute of Pathology. He is currently Professor of Head and Neck and Cardiothoracic Pathology at the David Geffen School of Medicine at UCLA. In addition, his interests also include molecular mechanisms of lung, head and neck tumors, and fibrosing interstitial pneumonia, and his basic research is focused on delineating the regulation mechanisms of voltage-gated cardiac ion channels.
Abstract:
Epidermal growth factor receptor (EGFR) gene mutational analysis and anaplastic lymphoma kinase (ALK) gene rearrangement detection are standard for guiding the treatment of advanced-stage lung adenocarcinoma. The lung biopsy specimens may contain a limited number of tumor cells for extracting enough DNA for gene mutational analysis, or performing fluorescence in-situ hybridization (FISH)to determine the genetic translocation.Immunohistochemistry (IHC) may be an alternative approach. Studies were performed to further validate the sensitivity and specificity of the antibodiesagainst EGFR with del E746-A750 in exon 19 and L858R in exon 21 or ALK, and to determine if the immunostaining withthese antibodies is a reliable screening method in the detection of these two genes’ abnormalities in the biopsied and resected lung adenocarcinomas. Sections from the tumor specimens were immunostained with these antibodies and the same specimens were used for DNA purification, analysis for EGFR mutations, and FISH for the detection of ALK rearrangement with break-apart probes. Based on the molecular testing, the overall sensitivity and specificity are high for antibodies against EGFR with del E746-A750 and L858R mutations and ALK. IHC is a very useful screening method for detecting EGFR gene mutation and ALK gene rearrangement.
- Young Research Forum
Chair
Gerard Lozanski
The Ohio State University, USA
Session Introduction
Kamakshi Worah
Mahatma Gandhi Missions Medical College and Hospital, India
Title: Exfoliative cytology of precancerous and cancerous lesions of cervix
Time : 09:00-9:15
Biography:
Kamakshi Worah has completed her MBBS from Vinobabhave University, Jharkhand, India. He is currently doing her pathology residency from MGM Medical College and Hospital, Navi Mumbai, India.
Abstract:
Present study was aimed to observe the varying trends in dysplasia and cancer of cervix in cytologically screened population of women attending the gynaecology outpatient department. Smears were prepared by using the swab techniques, the cervical os and ectocervix were then scrapped with the same applicator. Cells on the cotton tipped swab were spread on one clean glass slide, the slide was immediately placed in fixative solution of absolute alcohol. The smears were then stained by papanicolaou staining method. About 3991 patients were screened above the age group 20 years. About a third (34.6%) of women had normal cytological smears. A large portion of women had cytological finding consistent with inflammatory changes. Smears from 143 women (3.6%) revealed various grades of dysplasia and 17 (0.4%) women had features suggestive of malignancy. The frequency distribution of all cervical intraepithelial neoplasm and cervical cancer was found to be CIN1- 38.7%, CIN2- 26.9%, CIN3-23.7% and cancer 10.6%. The present study reveals that 84.4% of all CIN1 cases were in the age group of 30-59 years. 74.4% of CIN2 and CIN3 cases were in the age group 40-69 years. The commonest symptom in all cervical neoplasm was white discharge and the commonest sign being cervical erosion in CIN and growth on cervix in cervical cancer. Exfoliative cervical cytology has come a long way with newer and better techniques, better knowledge of risk factors, earlier detection of cancerous and precancerous lesion of cervix and thus more effective control of a once fatal disease.
Patricia Bacus
University of Alberta, Canada
Title: Bioprinting organs one step at a time: The special challenges of the 3D printed kidney as reflected in morphology
Time : 09:15-9:30
Biography:
Patricia Bacus is in her final year of a Bachelor of Science at the University of Alberta. Research interests involve anything neuroscience related and currently looking at sensorimotor integration but recently has found a flare for pathology. In her spare time Patricia participates in Student Governance and program planning for a variety of student groups.
Abstract:
Technology is playing a huge role in setting the future of society and medicine and with the many innovations that come medicine has had to adjust and keep up with the latest tools, methods and techniques. 3D printing has stopped being about just printing neat plastic objects but has evolved into bioprinting with a precision for biological material, biochemical and living cells ensuring the spatial components are proper for functional need and ability of the organ. It has gone from bioprinting two dimensional tissue and hollow tubes to making development for solid organs. Stem cells play a crucial role in the regeneration processes in the human body and recent research has shown that stem cells can be successfully used to assemble mini-tissue structures. In many organs like the liver and pancreas the function of the organ does not depend on a particular macroscopic structure and so making an organ by putting many mini-tissue structures together would work, as long as ducts and vessels are properly connected. However with the kidney the normal function of the kidney to concentrate the urine which is necessary to maintain life depends on the countercurrent multiplier and medullary osmotic gradient which can only be maintained with the normal macroscopic structure of kidney lobes and cortex, outer medulla and inner medulla. Without this concentrating ability of the kidney and normal macroscopic structure, the ability to produce hypertonic urine, all the body water would be lost via the urine and death would ensue. This need for a given macroscopic structure and for certain components to be in particular places in sequence for the whole structure to work is the reason why the 3D printed kidney remains the “moon shot”, the most difficult challenge in 3D printing of organs. Ultimately it is an achievable goal which will substantially improve medical care worldwide.
Sina Marzoughi
University of Alberta, Canada
Title: Cyborg Pathology and Humanity 2.0 - What will pathology be like in a world where fixing your body and fixing your computer become the same thing?
Time : 09:30-9:45
Biography:
Sina Marzoughi is a student in undergraduate neuroscience at the University of Alberta. He is the founder and executive director of the Edmonton World Health Organization Simulation (Edmonton WHO), a global health conference that provides opportunity for students to explore pragmatic global health challenges, approaches and solutions. He also has an interest in creating Smartphone applications for health education and already has two such applications published for the iPhone and iPad.
Abstract:
Biological evolution is slow. Brain implants and bio-artificial organs will be part of the near time evolution of human beings through technological improvements. As carbon based systems and silicon based systems increasingly merge in human patients of the future pathologists will learn to interpret the interface (brain computer interface) and combination of these two disparate world that they suddenly see looking down the microscope. There is already a very large cadre of people examining processed silicon under the microscope so it is not such a stretch to imagine this being incorporated into the job description of pathologists. The most promising bioartificial kidney uses silicon filter. Microscopic examination is a logical way to assess the "health" of the filter. It works both ways as increasingly cells are also being incorporated into computers. Right now the cell component of bio-artificial organs are encapsulated to prevent their escape into the body, and therefore hard to examine. But the health of these cells is very important to the function of the bio-artificial organ so eventually there will be means to examine them morphologically and this task will add to the richness of the pathologist's work experience. The brave new pathological world of Humanity 2.0!
Punit Virk
University of Alberta, Canada
Title: Transforming Pathology: Biotechnology as a positive feedback loop for the evolution of anatomical pathology
Time : 9:45-10:00
Biography:
Punit Virk is currently in the final year of his Bachelor of Science degree at the University of Alberta. He is the founder and advisor to the University of Alberta’s Partner’s In Health chapter. His current research interests involve the exploration of genetic therapies for highly pathological, rare genetic diseases like Fibrodysplasia Ossificans Progressiva. Punit has sat on advisory committees for undergraduate biology textbook development and teaching and learning in Science.
Abstract:
Many are familiar with the Moore's law exponential curve of price performance of computing and the extension of its influence over the world, in general. This idea is rooted in the belief that machines will be smarter than the whole human race combined in 2045 and will possess the means to take over the future agenda of the world. Moore's law in muted in medicine due to regulatory and safety considerations. So what stimulates exponential change in pathology? What are the drivers and inhibitors? Are our digital pathology systems going to wake up some day soon and tell us they can do our work better than we can? Will they be right about that? How much of a pathologist's work can only be done by a human being? When does the permanent vacation for flesh and blood pathologists begin? We all have a stake in the answers to these questions which pathologists seem to have been reluctant to ask until now!
Rongjia Liu
University of Alberta, Canada
Title: Consensus generation in pathology. Mentoring aspects and how rules are established, the example of Banff Transplant Pathology Meeting discussions
Time : 10:15-10:30
Biography:
Rongjia Liu is currently studying in the nutrition and dietetics program at the University of Alberta, in Edmonton, Alberta, Canada. She is interested in the connection between human nutrition and health and aspires to become a registered dietitian after graduation. Rongjia works with Dr. Solez on many of his projects, including planning for the upcoming 2015 Banff Transplant Pathology meeting in Vancouver, videography for the course LABMP590 on technology and the future of medicine, and assisting with the weekly pathology-nephrology clinical rounds at the University of Alberta hospital. Rongjia enjoys cooking, playing badminton, reading, and volunteering in her free time.
Abstract:
From its beginnings in 1991 the Banff Transplant Pathology meetings have used physician led consensus generation which is very different from the professional facilitator led consensus generation usually employed. The success of this approach over twenty-four years speaks for itself. There is a literature on such expert led consensus generation which outlines the approach which has been taken in the meeting. Kaner’s 2007 book Facilitator’s Guide to Participatory Decision-making, 2nd ed page 59 "Listening with a Point of View", states that these steps should be employed by the expert facilitator: 1) Raise the issue. State your position, 2) Ask for reactions, 3) Respond as a facilitator would by drawing people out and paraphrasing what they are saying; err on the side of more drawing people out, 4) After at least two moves of facilitative listening, give yourself the floor to speak, explain your perspective, answer questions, explain, advocate as needed, 5) Repeat steps 2-4 as needed remembering to balance your own point of view with at least twice as much facilitative listening. These skills and how to follow these five steps are now being passed on the new generations of pathologists as the Banff consensus generating process continues to evolve and expand through successive meetings and mentoring cycles within the framework of the newly formed Banff Foundation for Allograft Pathology.
Korey Fung
University of Alberta, Canada
Title: Genomic Pathology and Tissue Engineering Pathology compared and contrasted
Time : 10:30-10:45
Biography:
Korey Fung is an undergraduate student in the Nutrition and Food Sciences program at the University of Alberta. His current academic interests involve Global Health and Food Sensory Perception. He plays an important role assisting Dr. Solez in the Technology and Future of Medicine course and in the organization of the upcoming 2015 Banff Transplant Pathology meeting in Vancouver and other related matters, including the technical support for NKF cyberNephrology Email discussion groups, such as the the 2200 member RENALRD group for renal dietitians across the world. In addition to his academics, Korey is an avid cook, artist and violinist.
Abstract:
Technology in genome sequencing is expanding at an exponential rate. Already this technology has revolutionized cancer pathology. A new era of Genomic Pathology is upon us where we see much earlier disease diagnosis and personalized patient treatment programs. However there is a discrepancy in the field between the rapidly advancing genome technology and available pathologists who are qualified in the practice of using the genomic data as a means to identify and diagnose disease and as an adjunct to conventional anatomical pathology. Pathologists have had to relearn genetics! New classifications will need to be devised because in some instances the genomic differences may prove to be more important than previously noted anatomical differences. On the other hand the tissue specimens themselves have remained much as in the past in Genomic Pathology and it has remained mainly adjunctive to conventional pathology. Contrast that then with what Kim Solez has called Tissue Engineering Pathology, specimens coming from stem cell generated organs and regenerative medicine. Here the specimen type itself is brand new and some of the anatomical abnormalities observed are also without past precedent. New classifications will need to be devised. It is a brand new area of pathology practice, not adjunctive. Both Genomic Pathology and Tissue Engineering Pathology will become routine parts of mainstream pathology practice in the next decade.
Abhinav Walia
Mahatma Gandhi Missions Medical College and Hospital, India
Title: Comparative study of conventional pap smear versus manual liquid based cytology in screening of cervical cancer
Time : 10:45-11:00
Biography:
Abhinav Walia has completed his MBBS at the age of 24 years from Rajiv Gandhi University of Health Sciences, Bengaluru, India.He is currently pursuing his residency in MD Pathology at MGM Medical College, Navi Mumbai, India. He has participated and presented posters and oral papers in various conferences and workshops across India. He is exploring the possibility of adding value to his knowledge and curriculum by participating in various ongoing Pathology conferences and workshops across the globe.
Abstract:
Cervical cancer is one of the leading causes of cancer deaths in the world. India accounts for one fifth of the world’s burden of cervical cancer. Cytology screening by the Papanicolaou smear remains the main stay for control of cervical carcinoma. Liquid-based cervical cytology was developed to improve the diagnostic reliability of Conventional Pap smears. The present study was undertaken to evaluate a manual liquid based cytology technique (SurePath) and to compare the sensitivity of LBC with conventional Pap smear. The aim of the study was to compare the cytomorphology of conventional pap smears and manual liquid based cytology smears and to find out whether manual liquid based cytology method can be established for routine use in our laboratory setup. In the present study cervical smears were collected by the gynaecologist using Ayre’s spatula for the conventional Pap smear method and using SurePath cytobrush for manual liquid based cytology technique. 200 cases were examined for cytomorphological parameters. The details regarding cell size, cytoplasmic and nuclear details were studied for making the diagnosis. The observed results indicated that women screened with an LBC sample had significantly decreased detection rates of inadequate smears and increased detection of low-grade squamous intraepithelial lesion (LSIL)/ atypical cytology. Cells were better preserved and not obscured by blood, mucus, or inflammatory cells. The results showed increased sensitivity of LBC without loss of specificity. Liquid based cytology improves the quality of the sample and reduces the likelihood of false negative cytology results. Thus it will significantly improve early detection and treatment of cervical lesions.
- Track 7: Anatomical Pathology
Track 8: Surgical Pathology
Session Introduction
Petro O Vavrukh
I.Ya. Horbachevsky Ternopil State Medical University, Ukraine
Title: Cytometric analysis of cells in the glandular ductal epithelium of breast cancer
Time : 11:00-11:20
Biography:
Petro Vavrukh has completed his Ph.D at the age of 27 years from Danylo Halytsky Lviv National Medical University (Ukraine). He is the associate professor of pathological anatomy, dissection course and forensic medicine departments of I. Ya. Horbachevsky Ternopil State Medical University (Ukraine), pathologist in Ternopil Regional Bureau of Pathologists, Ternopil (Ukraine). He has published more than 20 papers in reputed journals. Member of the European Society of Pathology and Association of Pathologists of Ukraine
Abstract:
Background: The problem of Breast Cancer (BC) is one of the most important in modern oncology, due to its large spread in many countries of the world, where it took first place in the structure of malignancies in women. Aim: The aim of our work was to create an expert system for the diagnosis of breast cancer (separate morphological form) based on aggregate quantitative traits atypia cells. Materials & Methods: The object of the study was the nucleus and cells of glandular epithelium from punctured material of a ductal breast cancer for cytology. Light morphometry was performed by computer analyzer color images based on global microscope «Bresser» made in Germany, digital camera Leica DC 200 frames and grips (Leica, Germany) lens x 40. For morphometric study used a software tool AMS. It was used for measuring the area of cells, their nuclei and cytoplasm, calculating nuclear-cytoplasmic ratio. The measurement results are transferred to the metric system by aligning digital camera. 50 Nucleus were calculated in each of cytological preparations, and then a mean value of individual parameters was defined. The total sample size was approximately 5000 nuclei. Each kariometric parameter was tested by the expert system on cytologic specimens with breast cancer. We tested 70 cytological preparations with confirmed histologic diagnosis. These punctate swabs selected for testing were processed by computer image analysis. Then on the basis of cytometrix data for each case were calculated quantitative parameters, which values were compared with deciding criteria which are specific to breast cancer. The test results were determined informativeness of each parameter. Evaluation of informativeness was performed by calculating accuracy, sensitivity and specificity. Express-system, which included standard matrix (S-matrix) – the basis of diagnostic criteria for breast cancer, has been made to automate the process of diagnosing. Benchmarks and mathematical transformation (calculation of average values, plotting histograms, the distribution area of the nuclei and cytoplasm) were transformed into quantitative parameters that adequately describe the abnormal cell nuclei. The parameters which were obtained have been automatically introduced in the X-matrix constructed in the same format as the S-matrix. Then the computer program in real time comparing elements (quantitative parameters) obtained by X-matrix with elements S-matrix. The program is logged by coincidence x element of the corresponding s element. When the value of the X matrix fell in the range of S matrix elements coefficients corresponding cytometryx parameters were match. Diagnostic index was calculated as the sum of the coefficients cytometryx parameters that fell into the range of values for the S-matrix. In our cases, the clinical trials of the expert system, it was found that out of 14 cases of malignant disease of the breast diagnostic index was 70%.
Uzma Bukhari
Dr. Ziauddin Hospital, Pakistan
Title: Frequency of non Hodgkin’s lymphoma in a tertiary care hospital of Pakistan
Time : 11:20-11:40
Biography:
Uzma Bukhari has completed MBBS from Liaquat University of Medical and Health Sciences Jamshoro. She has completed MPhil histopathology from Karachi University Pakistan. She has been completed residency in FCPS (Fellow of college of physician and surgeon Pakistan) from Dr. Ziauddin hospital Karachi and going to appear in exam this year. Currently she is working in histopathology clinical laboratory of Dr. Ziauddin hospital. She has published 10 research papers and one paper has been published internationally.
Abstract:
Objective: The objective of the study was to determine the frequency and pattern of non Hodgkin’s lymphoma (NHL) in adults in a tertiary care hospital. Material & Methods: This retrospective study was conducted at Histopathology Department, Dr. Ziauddin Hospital over a period of 09 years, from 2005 to 2013. 192 cases of Non Hodgkin’s lymphoma (NHL) were retrieved from surgical pathology record. After routine H & E stain examination, a panel of immunohistochemical stains was applied on formalin fixed paraffin embedded tissue. The data was analyzed for type of lymphoma, age & sex distribution, site of biopsy and immunophenotypic features. Results: Out of 192 cases of non Hodgkin’s lymphoma (NHL), 132 (69%) were males & 60 (31%) were females. Mean age of patients was 46.7 years and median age was 47 years. B cell lymphoma was out numbered (87%) than T cell lymphoma (13%). Diffuse large B-Cell lymphoma was the commonest (113) B cell lymphoma followed by other types of lymphoma. 52% cases were from extra nodal sites followed by 34% of nodal lymphoma. Site of biopsy was not mentioned in 14% cases. Conclusion: In adults, B cell lymphoma is more frequent than T cell lymphoma with diffuse large B-cell lymphoma being the commonest non Hodgkin’s lymphoma.
Zhi Dai
Fudan University
China
Title: MicroRNA-29a drives DNA hypermethylation and metastasis of hepatocellular carcinoma by targeting TET family members
Time : 11:40-12:00
Biography:
Abstract:
Background & Aims: Ten eleven translocation (TET) enzymes convert 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) and play crucial roles in biological and pathological processes by mediating DNA demethylation; however, the functional role of this epigenetic mark and the related enzymes in hepatocellular carcinoma (HCC) progression remains unknown. Methods: We analyzed 5-hmC levels using tissue microarray from a 323 HCC patient cohort. We determined RNA expression levels of TET family proteins, the TET expression-silencing microRNA-29a, and suppressor of cytokine signaling 1 (SOCS1) in 108 HCC patients. The methylation status of SOCS1 promoter was examined using glucosylation of genomic 5-hmC followed by methylation sensitive polymerase chain reaction (glucMS-qPCR). We determined miR-29a and TET family members’ functional effects using RNA interference and transgenic expression in HCC cells and evaluated xenograft tumor growth in nude mice. Results: TET family enzymes down regulation is one likely mechanism underlying 5-hmC loss in HCC. There was a significant inverse correlation between miR-29a and TET expression in HCC tissues. Dot blot assay revealed that miR-29a up regulation and down regulation in HCC cells yields distinct global DNA hydroxymethylation patterns, and that increased DNA methylation of SOCS1 promoter is associated with miR-29a overexpression in HCC cells. Furthermore, miR-29a silencing anti-metastatic SOCS1 through direct TET family targeting, resulting in SOCS1 promoter demethylation inhibition. Finally, miR-29a overexpression correlates with poor clinical outcomes and TET-Family-SOCS1-matrix metalloproteinase (MMP) 9 axis silencing in HCC patients. Conclusions: These findings demonstrate that 5-hmC loss is an epigenetic hallmark of HCC, and miR-29a is an important epigenetic modifier, promoting HCC metastasis through TET family targeting. Moreover, these results offer a new strategy for epigenetic cancer therapy.
Makari Hanumanthappa K
IDSG Government College
India
Title: Bacteriophages as natural antimicrobial agents against phytopathogenic Ralstonia solanacearum: A novel alternative to antibiotics
Time : 12:00-12:20
Biography:
Makari Hanumanthappa K has completed his MSc Biotechnology in 2003 from Kuvempu University and MPhil in 2008. He is serving as Assistant Professor and Head in Department of Biotechnology, IDSG Government College, Chikmagalur, India. He has published more than 30 research and review papers in reputed journals and has been serving as reviewer for many scientific journals. He is a fellow member for various national and international scientific organizations. He is the recipient of Environmentalist-2010 award for his outstanding research contribution in Microbial Biotechnology from National Environmental Science Academy, India. He is pursuing PhD in Microbiology from Bharathiar University.
Abstract:
Bacteriophages are the natural bacterial killers and viruses of prokaryotes. Phage infects the bacteria more specifically, causes lytic or lysogenic activity in cells. Research on phages is a fast expanding area in plant protection. Several experiments have shown phage mediated bio- control of bacteria. Ralstonia solanacearum is a phytopathogenic, Gram-negative bacterium causes wilting symptoms in many solanaceous vegetable crops including potato and ginger. It infects to roots and specifically invades in the plant tissue, extensively multiplying in xylem part of the plant leads to wilting, resulted heavy economic losses to the farmer. The chemical control of bacterial infections inside plant tissue is unsuitable and inaccessible since high multiplication rate and colonizing deeper inside the plant tissue. Use of synthetic antibiotic for the control of bacteria has been resulted increased antibiotic resistance. Therefore, in the present investigation an attempt was made to isolate bacteriophage against R. solanacearum. The aim of this research work was to isolate and characterize lytic bacteriophages against R. solanacearum. The phytopathogenic R. solanacearum was isolated from infected potato and ginger plants. The PCR and 16S rRNA sequence analysis were used for the identification of the bacteria. Four bacteriophages Ï•RsA1, Ï•RsB1, Ï•RsC1 and Ï•RsD1 were isolated specific to R. solanacearum. The electron microscopic analysis was done to observe morphology and RAPD analysis was conducted to identify genetic diversity of phages. In-vitro confirmation phage activity against bacteria was done. The results of the study greatly anticipated that phages can be used as potent antimicrobial agents in plant protection.
Momoh Martins
Babcock University
Nigeria
Title: Autopsy prevalence of gastroesophageal reflux disease
Time : 12:20-12:40
Biography:
Dr. Martins Momoh 47years old, from Edo state Nigeria, west Africa. He had early education in edo state Nigeria. Attended University of Lagos, graduated with MBBS in 1994. Served as a medical officer with National Orthopaedic Hospital Igbobi from 2000 to 2006. Proceeded to National post graduate medical college of Nigeria, for residency training in histopathology with lagos university teaching hospital training point and graduated with FMCPATH in 2013. Presently a Lecturer, consultant pathologist and Head Histopathology department Benjamin Carson School of Medicine, Babcock University Ilishan Remo Nigeria. Am married to Eunice and blessed with children.
Abstract:
INTRODUCTION Gastro-esophageal reflux disease (GERD) is relatively rare in Nigeria. There is paucity of data regarding its prevalence in Nigeria. Recent population based studies have shown that it is on the rise; and with this may come the risk of progression to Barrett’s esophagus and a potential of progressing to esophageal adenocarcinoma. The aim of this study is to determine the autopsy prevalence of gastro esophageal reflux disease (GERD) at LUTH. Materials and methods histopathological analysis of paraffin-embedded tissues stained with hematoxyllin and eosin as well as special stains like PAS, Alcian blue and Giemsa were used on the gastro esophageal samples from 100 autopsy cases. Representative gastric samples were also examined. Results The prevalence of GORD in this study was thirteen percent and no case of Barrett oesophagus and dysplasia was recorded. Conclusion Gastro esophageal reflux disease has thus shown an apparent increase in prevalence compared to previous studies. More clinico pathologic study will be required to confirm this assertion.
- Track 1: Molecular Pathology
Chair
Kim Solez
University of Alberta
Canada
Co-Chair
Peter L Nagy
Columbia University
USA
Session Introduction
Peter L Nagy
Columbia University, USA
Title: Optimizing sensitivity and specificity of clinical next generation sequencing in constitutional and cancer applications
Time : 10:40-11:00
Biography:
Peter L. Nagy received his MD degree from the University ofPecs, Hungary in 1989. His interest to pursue a career as a physician scientist led him to Purdue University where he earned his Ph.D. in Biochemistry. He worked under the mentorship of Dr. Howard Zalkin and made important discoveries relating to C1-metabilism in bacteria. Subsequently he completed Anatomic and Molecular Genetic Pathology training and Stanford University as well as postdoctoral training in Michael Cleary’s laboratory. He was the first to purify and functionally characterize the Set1 histone methyltransferase complex from S. cerevisiae in collaboration with Dr. Roger Kornberg. He co-developed the FAIRE method with Jason Lieb allowing physical fractionation of chromatin based on formaldehyde crosslinkability. Currently he leads a research laboratory investigating the role of transcriptional defects in neurodegenerative diseases, such as AOA2 and ALS4, and is director of the clinical next-generation sequencing facility in the Laboratory of Personalized Genomic Medicine at Columbia University Medical Center in the Department of Pathology and Cell Biology.
Abstract:
Our Laboratory of Personalized Genomic Medicine (LPGM) at Columbia University Medical Center started to offer clinical whole exome sequencing (WES) in January 2013 and clinical cancer whole exome/transcriptome(CWES) sequencing since January 2014. We processed and issued reports on over 500constitutional and about 100 cancer cases. The majority of these samples are from the pediatric population (>80%) both for constitutional and cancer testing. Of the cases analyzed to date we have identified pathogenic or probable pathogenic mutations responsible for the patients’ condition in about 30 percent of the cases and changed clinical management of pediatric malignancies in about 20 percent of our patients. The fact that a large percentage of cases remain without molecular diagnosis or useful clinical treatment recommendation indicates that we need to improve our assignment of pathogenic effect to mutations in genes not previously linked to disease. We have developed a database we refer to as “SNP-catcher” that integrates patient information with a molecularsystems approach to evaluate the significance of mutations. Such systems driven analysis of clinical exome and transcriptome sequencing data is an important step in the accelerateddiscovery of novel disease causing genes and disease mechanisms and obtaining useful treatment recommendations. Through my presentation the audience will obtain an understanding of the current state of the art of clinical genomic testing; will become familiar with the major factors that determine the precision and sensitivity of pathogenic mutation detection; have a thorough understanding of the importance of proper implementation of structural and functional basic science data sources into the clinical analysis pipeline. I will outline the contribution of clinical data collection to discoveries in basic science and review the obstacles to and opportunities for more efficient collaboration between clinical medical centers and the pharmaceutical industry.
Bonnie E Gould Rothberg
Yale University, USA
Title: Custom AmpliSeqâ„¢ targeted resequencing to identify novel clincopathologic correlates in early-stage lung adenocarcinoma: A yale lung cancer biorepository study
Time : 11:00-11:20
Biography:
Bonnie E Gould Rothberg is a Molecular Cancer Epidemiologist and Assistant Professor within the Department of Oncologic Research at the Yale Cancer Center with secondary appointments in the Departments of Chronic Epidemiology and Pathology at the Yale School of Medicine. She completed her MD (1994), MPH (2005) and PhD (2009) all from Yale University and joined the Yale faculty in 2011 following a 2-year postdoctoral fellowship. Her lab is invested in leveraging Ion Torrent targeted-resequencing to identify both germline and somatic genetic variation that are prognostic for early-stage cancers where, despite a curative-intent margin-free resection, the median 5-year survival rates approach 50%. She has also built and still serves as the inaugural Medical Director for the Yale Lung and Gastrointestinal Cancer Biorepositories, which combine biospecimen best practices with rigorous and robust clinico-epidemiologic annotations useful for evaluating gene-environment interactions that influence cancer outcomes. She has published over 30 manuscripts related to her work.
Abstract:
The 5-year survival for Stages I/II lung adenocarcinoma (L-ADC) (60,500 US cases annually) following curative-intent complete resection and, where indicated, adjuvant chemotherapy, ranges from 36% (Stage II) to only 80% (Stage IA). Although evaluation of EGFR and KRAS somatic mutations in early-stage L-ADCs is now common, clinicopathologic correlates and associations with prognosis are incompletely understood and the correlates of less common driver mutations and frequent passenger mutations (e.g., STK11, p53) are only emerging. To better characterize the clinicopathologic correlates of L-ADC somatic mutations, we have coupled an ongoing prospective cohort study of early-stage L-ADC patients treated with curative-intent surgery at Yale-New Haven Hospital with a robust, novel next-generation DNA sequencing and analysis pipeline. Eligible participants are enrolled into the Yale Lung Cancer Biorepository, a Biobank that couples biospecimen best practices for both fresh and formalin-fixed materials with comprehensive clinico-epidemiologic annotations for each participant both at intake and at regular follow-up. Genomic DNA from both tumor and germline is prepared using the Ambion RecoverAll DNA preparation kits and quantified using an RNAse P standard. Ten ng is subsequently used for each of 3 pools from a customly constructed Ion Torrent AmpliSeqTM panel that targets 93 genes where the published literature supports a significant role for somatic mutations in L-ADC biology. Following emulsion PCR and sequencing on the Ion Torrent PGMTM next-generation DNA sequencer, resulting BAM files are processed through a novel front-end bioinformatics pipeline that specifically adjudicates each sequencing run to identify and eliminate from subsequent analyses runs not meeting specific qualifying criteria. Next, variants are aligned from matched germline and tumor samples, and, among tumor-specific variants, the non-synonymous coding mutations are further pursued, being organized according to functional roles within genes and pathways with these summary data arrayed into a data matrix for subsequent statistical analysis. This talk will focus on our uniquely comprehensive method, while highlighting results from our preliminary analyses.
Claudia Kappen
Pennington Biomedical Research Center, USA
Title: Molecular pathology of diabetic embryopathy in mouse models
Time : 11:20-11:40
Biography:
Claudia Kappen received her doctorate from the University of Cologne, Germany, followed by postdoctoral training at Yale University. She since directed independent research laboratories at Mayo Clinic Arizona and University of Nebraska Medical Center, rising through the ranks to Full Professor, and currently holds the Peggy M. Pennington Cole Endowed Chair in Maternal Biology at Pennington Biomedical Research Center in Baton Rouge, Louisiana. She has 60 publications listed in PubMed, received the James G. Wilson Publication Award from the Teratology Society in 2009, co-edited a special issue "Neural Tube Defects" for the journal Birth Defects Research, and serves as Associate Editor for the journals Reproductive Toxicology and PLoS One.
Abstract:
Maternal diabetes during pregnancy is a well-known risk factor for a spectrum of structural birth defects in the offspring, collectively addressed as diabetic embryopathy. Heart defects and neural tube defects are the most common malformations, but craniofacial defects, caudal growth defects and either small or large-for-gestational-age are also characteristic outcomes. It is believed that the latter two conditions also constitute risk factors for cardiometabolic disease later in life. Using mouse models, my research program investigates the underlying molecular mechanisms for abnormal development in utero, with particular focus on neural tube defects. Embryos exposed to maternal diabetes in utero are smaller, which is associated with placental abnormalities and altered gene expression. Microarray and in situ hybridization studies identified abnormalities in proliferation and migration of spongiotrophoblasts, which are a source of intrauterine nutrition. The exposure also alters gene regulatory programs in the developing embryo, particularly affecting the expression of known genes that have a role in neural tube closure. Evidence from chromatin-immunoprecipitation, followed by nextgeneration sequencing, implicates epigenetic changes as the underlying molecular mechanism. We have recently shown that the neural tube closure defects in the diabetic models are preceded by impairments in gastrulation, the critical process during which cells for all three germ layers are specified. These early abnormalities, for the first time, provide a unifying molecular and cellular explanation for the seemingly unconnected phenotypic defects in diabetic embryopathy.
Richard Y Zhao
University of Maryland, USA
Title: Inroads to personalized medicine through molecular pathology
Time : 11:40-12:00
Biography:
Richard Y. Zhao, a Molecular Pathologist, is a Tenured Professor of Pathology, Microbiology-Immunology and Human Virology at the University of Maryland School of Medicine. Dr. Zhao is also the Division Head of Molecular Pathology in the Department of Pathology, Director of Translational Genomics Laboratory in the School of Medicine, and Director of Molecular Diagnostics Laboratory at the University of Maryland Medical Center. Dr. Zhao’s clinical expertise is in the area of molecular pathology and personalized medicine. His basic science research interests are in HIV/AIDS, cancer biology and nanoparticle-based single molecule detections. Dr. Zhao has published over one hundred scientific papers and has served on numerous scientific editorial boards including Clinical and Applied Immunology Reviews, Clinical Laboratory Science, Cell Research, Cell and Biosciences, Chinese Journal of Clinical and Experimental Virology, Journal of Clinical and Experimental Pathology, Frontiers in Virology, Microbial Cell, PLoS One and Retrovirology. He has been invited to review scientific grant applications for funding agencies of over 10 different countries and has chaired a number of NIH grant review study panels. He has been invited to give scientific and clinical lectures world-wide.
Abstract:
Advances in human genome analysis, OMICS science and big data analysis continue to make inroads for molecular pathology to assist in personalized medicine. Through proper analytical and clinical validation, many of those newly discovered biomarkers such as SNPs/SNVs and INDELs that are associated with specific diseases or responses to various drug therapies, could be used to develop new molecular diagnostic tests for prediction, diagnosis, treatment and monitoring of various diseases. Since these molecular-based testing can be used to assess individual’s genetic variability and probability for onset of certain diseases or responses to various drug therapies, customized treatment plan or therapies could be designed specifically for each individual patient. As more and more medical professionals realize the benefits of being able to use these useful molecular pathology tools for precision medicine, personalized patient care through individualized molecular pathology testing is no longer a future perspective but rather a reality in many of the major medical centers in the United States including the University of Maryland School of Medicine and Medical Center. There is no doubt that individualized molecular testing will soon become a routine clinical practice for personalized patient care world-wide. However, successful transition of such a paradigm shift from traditional medicine to personalized medicine requires integrated and concerted effort from all allied medical professionals. Education and continued education of healthcare administrators, physicians, medical practitioners and laboratory personnel on the pharmacogenomic testing and associated patient care are among the essential steps for successful transition and implementation of personalized medicine. This lecture will introduce some of the key factors associated with this paradigm shift from current medicine to personalized medicine, review different categories of pharmacogenomic testing that are designed for personalized healthcare. Specific case reports will be presented drawn from our own experiences on how individualized molecular testing has helped us in our clinical practice and personalized patient care. Future perspectives on this exciting new area of molecular pathology and medicine will also be discussed.
R. Rajesh Singh
University of Texas, USA
Title: Rapid progress of next generation sequencing technology: Implications for implementation in clinical diagnostic laboratories
Time : 12:00-12:20
Biography:
Rajesh Singh has a PhD in Biochemistry from The University of Mysore, India and Postdoctoral research experience from University of Texas, MD Anderson Cancer Center. He has extensive experience in cancer biology focusing on the deregulated oncogenic and tumor suppressor pathways in the origin and maintenance of solid tumors and hematological malignancies. He is an Assistant Professor and Director Clinical NGS Development in the molecular diagnostics laboratory at MD Anderson, where he supervises the design and validation of the NGS assays for routine mutational screening of tumors. He has published more than 40 papers and 3 review articles in reputed journals.
Abstract:
In the past few years, the massively parallel sequencing capabilities of NGS have found widespread acceptance for clinical genomics in molecular diagnostic laboratories. Due to rapid progress, the underlying technology and the associated informatics is constantly evolving resulting in considerable process improvements in relatively short durations. Although desirable, these constant upgrades pose a challenge for clinical sequencing assays being used for clinical purposes due to the need of through validation before implementation. Here, in the context of a CAP and CLIA accredited molecular diagnostic laboratory the advantages and challenges posed by the constant upgrades for routine NGS testing of solid tumors and hematological malignancies will be presented. The progress in the wet bench and informatics portions of major NGS platforms will be highlighted.
Wenqing Cao
University of Rochester School of Medicine and Dentistry, USA
Title: Ampullary tumors and tumor like lesions: Histological classification, diagnosis and treatment options
Time : 12:20-12:40
Biography:
Wenqing Cao, MD is a gastrointestinal Pathologist and Assistant Professor at University of Rochester Medical Center. She received her Medical Degree from Tongji Medical University, China in 1992. She completed Anatomic and Clinical Pathology Residency at Northwestern University in 2009 and Gastrointestinal Pathology Fellowship at the Mount Sinai Medical Center in 2010. Since 1998, she has done extensive basic and clinical translational research in GI malignancies. She has published more than 20 papers in reputed journals and has been serving as an editorial board member.
Abstract:
The ampulla of Vater is a complex region adjoined by three distinct anatomic structures: common bile duct, pancreatic duct and duodenum. This region is lined by mixed intestinal and pancretobiliary-type epithelium. Adenomas and adenocarcinomas are the predominant ampullary tumors. Endocrine tumors are rare, which comprise of benign carcinoids and malignant neuroendocrine carcinomas. Benign tumor like lesions constitute a heterogeneous group of entities that includes primary sclerosing cholangitis, recurrent pyogenic cholangitis, inflammatory myofibroblastic tumor, and recently recognized IgG4 related sclerosing cholangitis. Stricture and obstructive jaundice are the most common presentations in ampullary tumors and tumor like lesions. Despite the advances in imaging techniques, discriminating ampullary carcinoma from benign tumors and tumor like conditions is still challenging. Identifying IgG4 sclerosing cholangitis is particularly important as the disease is responsive to steroid treatment. Immunohistochemical stains can be helpful for histological diagnosis and staging but they have limitations. The current classification system for ampullary carcinoma has limited value of predicting prognosis. Recent studies have suggested histological differentiation (intestinal type vs pancreatic type) and sub-location (intra-AMP, AMP-ductal, peri-AMP-duodenal and AC-not otherwise specified) of ampullary carcinoma have prognostic significance. The treatment for benign tumors and tumor like lesions is mainly local resection. Pancreatoduodenectomy is the most appropriate resectional procedure for large adenomas and early stage ampullary carcinomas whereas stent or surgical palliation may be offered for late stage unrespectable cancers. Adjuvant or neoadjuvant chemotherapy may benefit a subset of ampullary carcinoma patients. In this talk, we describe ampullary tumors and tumor like lesions, and summarize different histological classification systems for ampullary carcinoma. We also address the challenges in discriminating malignant and benign ampullary lesions, and introduce the potential biomarkers for early diagnosis and prediction prognosis. In the meantime, the classical and emerging treatment approaches will be illustrated.
Gabriela Oprea-Ilies
Emory University Hospital
USA
Title: Insulin-like growth factor 1 receptor expression in hormone receptor positive and negative breast carcinoma: A retrospective cross-sectional study
Time : 13:25-13:45
Biography:
Dr. Oprea-Ilies has a medical degree from The Institute of Medicine and Pharmacy, Bucharest, Romania. She completed pathology residency at the University of Minnesota, Twin Cities and Cytology fellowship at Emory University, Atlanta, GA. She studied breast cancer with Dr. Schnitt, Collins and Mallory, in Boston. Currently she is a pathologist, assistant professor and co-investigator of the breast tissue bank at Emory University, director of the Immunohistochemical laboratory at Grady Memorial Hospital and adjunct professor at Georgia State University. She has published in reputed journals, has been reviewing papers and serving in the editorial board member of repute.
Abstract:
Introduction: Breast cancer is the most common non-skin related malignancy in women in the USA accounting for 29% of newly diagnosed cancers. Its incidence increases with age. While its treatment is currently determined by expression of predictive and prognostic markers ER, PR and HER2, multiple signaling pathways are under "microscope" for their potential therapeutic relevance in cancer treatment. One of these pathways is the insulin-like growth factor pathway (IGF). Insulin-like growth factor-1 receptor (IGF-1R) is an important inhibitor of apoptosis and exerts a fundamental role in cell growth and malignant transformation. Prior studies have shown its role in breast tissue proliferation and overexpression in breast cancers. In this study we assessed the expression pattern of IGF-1R in different subtypes of breast cancers and explored its relationship with patient demographics, clinicopathologic variable and outcome. Design: Microarray were constructed from tissue of invasive breast carcinomas diagnosed during a period of 7 years. IGFR expression was studied by immunohistochemistry (IHC) and scored semi-quantitatevly, using 0-3 for intensity and percentage of tumor staining. IGFR expression was studied in relation to ER, PR and HER2 status. Results: Of the 350 invasive breast carcinomas, 327 stained positive for IGFR (93.4%). IGFR expression was prevalent in hormone receptor (HR) positive tumors (p<0.001) and was lower in triple negative tumors (TNT) than non-TNT (p=0.01). Independent of HR and HER2 expression, IGFR was expressed in 98.2% of breast cancer from Caucasian women vs. only in 90.8% in African-American women (p<0.001). IGFR expression was associated with lower histopathologic grade and smaller tumors (p=0.015). While, in our population HR-negative, larger tumors with higher grades were factors independently associated with worse PFS and OS, among Caucasian patients negative IGFR was associated with shorter OS (HR=7.12, p=-.005). No such interaction was found in AA patients. Conclusion: Due to its role in cancer progression and its presence in many breast tumors, IGF-1R offers a promising drug target. Currently, multiple drugs that target IGF-1R are under development. With its cross talk with the ER, IGF-1R constitutes a possible target in ER positive breast cancers. Additionally, some studies have shown that TNTs respond to anti-IGF-1R therapy. Understanding the expression patterns of IGF-1R would provide insight into tumor growth pathways and could lead to improved treatment of these cancers.
Kay Ohlendieck
National University of Ireland, Ireland
Title: Molecular pathogenesis of motor neuron disease as revealed by mass spectrometry-based proteomics
Time : 13:45-14:05
Biography:
Kay Ohlendieck has an undergraduate degree in Biology from the University of Konstanz, Germany (1985), a PhD in Biochemistry from University College Cork, Ireland (1989) and a D.Sc. in Muscle Biology from University College Dublin, Ireland (2011). He has worked as a postdoctoral associate at the University of Iowa, Iowa City and at the State University of New York, Stony Brook, as well as a Lecturer in the Department of Pharmacology, University College Dublin (1995-2001). Since 2002, he is Chair of Biology at the National University of Ireland, Maynooth, and his research focuses on skeletal muscle proteomics.
Abstract:
The heterogeneous group of neurodegenerative syndromes that encapsulates motor neuron diseasesare inherited or spontaneous disorders that are associated with progressive muscular atrophy. Our laboratory has initiated a proteomic profiling initiative to identify novel muscle-associated biomarkers of motor neuron disease using the wobbler mouse model of primary motor neuronopathy. We employed two complementary methods, fluorescence two-dimensional difference in-gel electrophoresis and liquid chromatography in combination with label-free mass spectrometry. The proteomic analysis of disease-induced muscular atrophy has revealed highly complex alterations in the abundance or isoform expression pattern of a large number of skeletal muscle proteins involved in cellular signaling, excitation-contraction coupling, the cytoskeletal network, ion homeostasis, energy metabolism and the cellular stress response. Interestingly, the complex changes in the muscle proteome due to the progressive degeneration of individual motor neurons appears to be considerably different to the more unilateral skeletal muscle transformationobserved in disuse-associated muscular atrophy or denervated muscle fibers. Hence, a subtype-specific vulnerability of neuromuscular synapses and compensatory mechanisms of fiber type shifting seem to exist in motor neuron disease as compared to other forms of muscular atrophy. The newly identified proteomic biomarker candidates of motor neuron disease may be useful for improving diagnostic, prognostic and therapeutic approaches.
Lihong Weng
City of Hope, USA
Title: Application of matrix – assisted laser desorption/ionization imaging mass spectrometry in glioblastoma
Time : 14:05-14:25
Biography:
Lihong Weng has completed her MD from Kiel University, Germany and postdoctoral studies from City of Hope, USA. Currently, she is working on identifying tumor related antigens and the biology function of engineered T CAR cells in Departments of Hematology & Hematopoietic Cell Transplantation and Cancer Immunotherapy & Tumor Immunology.
Abstract:
Glioblastoma (GBM) is the most common and fatal type of brain tumor. GBM tumors are highly heterogenous, containing genetic and molecularly distinct clones that confer an evolutionary advantage under the selective pressure imposed by therapies. This heterogeneity is one of the leading causes of treatment failure and tumor relapse for targeted therapies. Identification and quantification of the multiple tumor specific antigens in the context of GBM tissue is therefore essential to provide targets for combination treatments. Matrix–Assisted Laser Desorption/Ionization Imaging Mass Spectrometry (MALDI-IMS) is a novel technology that enables identification of specific molecules, such as proteins, glycans, lipids and other endogenous molecules directly on tissue sections. We tested human GBM tissues, tumor edges and normal brain controls to identify novel GBM specific antigens using MALDI-IMS. By mounting tissue sections with different type of matrices, we identified the profiles of peptides and lipids (<1200 Da), as well as the expression patterns of proteins (2000-25000 Da) in GBM tumor and tumor edges. Two candidates of interest (10094,92 m/z and 13785,47 m/z) were found highly expressed in GBM dense tumor regions, but not tumor edges. Interestingly, these two candidates were differentially distributed in the regions within the tumor tissue, and thus may mark different tumor cell sub-populations. Our results demonstrate the potential for MALDI-IMS for identifying tumor specific molecules that could be useful in the development of novel combinatorial GBM therapies. This MALDI-IMS extracted information also yields important insights into special and regional tumor heterogeneity within the context of the tumor tissue.
- Track 4: Clinical Pathology
Track 5: Renal Pathology
Track 6: e-Pathology
Chair
Kim Solez
University of Alberta
Canada
Co-Chair
K. H. Ramesh
Albert Einstein College of Medicine
USA
Session Introduction
K H Ramesh
Montefiore Medical Center, USA
Title: Significance of HER2 genetic heterogeneity detected by fluorescence in Situ hybridization analysis in invasive ductal breast carcinoma
Time : 09:50-10:10
Biography:
K. H. Ramesh did his PhD, in Human Cancer Cytogenetics from Bangalore University, India. He trained under the guidance of world renowned geneticist Avery Sandberg, MD., at Roswell Park Cancer Institute, Buffalo, USA. He is Board Certified in Clinical Cytogenetics; currently a Diplomate of the American Board of Medical Genetics and Genomics, and Fellow of the American College of Medical Genetics and Genomics. At present he is the Director of Cancer CytoGenomics and Associate Professor of Pathology at Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, USA. He has over 25 years of experience in Human Cancer Genetics
Abstract:
Breast cancer is the most common malignancy in women of all ethnicities. Standard treatment involves surgical resection; pathologic analyses that includes morphologic, immunohistochemistry (IHC) and Fluorescence In Situ Hybridization (FISH) analysis to determine ER, PR, and HER2 parameters in the tumor. The HER2 gene (17q11.2-12) is amplified in 20% of invasive breast cancers. Patients with tumor positive-HER2 gene amplification are eligible for adjuvant chemotherapy with Trastuzumab (Herceptin), resulting in longer survival. Studies have shown that 40% of breast tumors show genetic heterogeneity (GH) as per ASCO/CAP (2013) criteria. Breast tumors with an IHC score of 2+ qualify for FISH testing to rule out HER2 gene amplification, and if positive, patients are eligible for Herceptin treatment. GH is defined as the presence of >5% and <50% of 20 tumor cells showing HER2- amplification. The 40% of breast tumors that show GH pose an unresolved dilemma in treatment. Our aim is to establish the clinical significance of HER2 GH in breast cancer. Data is correlated with patient demographics, histological tumor type and stage, IHC scores, treatment regimen and morbidity to determine if GH has an impact on treatment modality. These outcomes include differences in survival (Kaplan-Meyer survival curves) and morbidity from the treatment (cardiomyopathy). Our hope is to determine whether a systematic study of outcomes among patients with HER2 GH with or without equivocal FISH results will address reconsiderations of treatment guidelines for these patients.
Maria Teresa Mascellino
Sapienza University of Rome, Italy
Title: Activity of a double-carbapenem association in the in vitro susceptibility of Carbapenemase-producing Klebsiella Pneumoniae
Time : 10:10-10:30
Biography:
Maria Teresa Mascellino has completed her MD at the age of 25 years from University "La Sapienza" of Rome and specialization studies in Clinical Microbiology and Infectious Diseases from University "La Sapienza" of Rome. She is Director of Microbiology Laboratory in the Department of Infectious Diseases. She has published more than 80 papers in reputed journals and has been serving as an editorial board member of repute. She is member of many scientific societies and has participated in relevant International Research Projects.
Abstract:
Klebsiella pneumoniae carbapenemase (KPC)-producing are associated with increased mortality due to the resistance to the most antibacterial agents. Pan-drug resistant (PDR) K. pneumoniae infections have been recognized as an emerging challenge worldwide, due to the lack of therapeutic options . Strains of third-generation-cephalosporin-resistant and carbapenem-resistant K. pneumoniae are rapidly spreading. Preliminary data suggest a role of unconventional antibiotic combinations against colistin-resistant carbapenemase-producing isolates (CP-Kp). Aim of our work was to study the infections due to carbapenemase-producing Kl. pneumoniae , associated with a high mortality rate, belonging to patients hospitalized in a tertiary care setting. In these cases the therapeutic options are limited especially when associated with colistin resistance. In this case , a double carbapenem regimen has been shown to be effective and safe. Herein, we evaluated through antibiotic kill studies the in vitro synergistic activity of meropenem plus ertapenem against MDR Kl. pneumoniae isolated from 3 patients with bacteraemia who were successfully treated with double-carbapenem therapy. The results of time killing analysis showed that ertapenem or meropenem alone exhibited an initial reduction in log CFU/mL followed by a significant regrowth at 24h in all the patients. When the double-carbapenem combination was assessed, a bactericidal and synergistic activity was achieved at 4, 6, 8 h and maintained at 24 h at concentrations of meropenem 0.5xMIC plus ertapenem 1xMIC, meropenem 1xMIC plus ertapenem 1xMIC and meropenem 2xMIC plus ertapenem 1xMIC in all the patients. In our patients, ertapenem plus meropenem induced clinical (defervescence in 48 h) and microbiological (absence of growth in blood cultures performed 48 h after therapy) responses. In the in vitro studies, combination treatment exhibited a higher bacterial killing than monotherapy, even in the presence of high carbapenem MICs. In all the isolates, the combination treatment maintained bactericidal effect up to 24h, thus confirming the clinical efficacy of this innovative regimen. In summary, this report suggests that meropenem plus ertapenem might be considered a promising option in CP-Kp infections, especially in patients for whom colistin treatment is inappropriate due to resistance or toxicity.
Kim Solez
University of Alberta, Canada
Title: Mentoring in pathology: review and case study with observations on Dunbar’s Number
Time : 10:45-11:05
Biography:
Kim Solez, M.D., FRCPC, Professor of Pathology at the University of Alberta, and President and CEO of Transpath Inc., is one of the world’s foremost kidney pathologists. He is the father of the Banff classification that sets standards worldwide for how biopsies from kidney and other solid organ transplants are interpreted, and started the post-earthquake disaster relief task force of the International Society of Nephrology. He is a popular blogger on internetevolution.com, and directs NKF cyberNephrology, a joint venture of the National Kidney Foundation (U.S.) and the University of Alberta. Kim has also created many educational videos for the Lifeboat Foundation
Abstract:
There have been many articles about mentoring but most deal with short-term effects and assume few mentors per person, and that mentoring is in the past and unidirectional. We present the forty-year mentoring influence of one physician researcher/kidney pathologist, Liliane Striker (1937-2004), on the career of another, Kim Solez. The application of the technological singularity to medicine, development of the Technology and Future of Medicine course, and expansion of Virchow’s Medicine Writ Large idea in Dr. Solez’s career can all be traced back to 1974 conversations between Drs. Striker and Solez. Now through Dr. Solez’s students one can imagine the influence of those 1974 ideas propagating for a hundred years or longer. Mentoring/influencing effects are active, ongoing, and in the present. The process involves not just conventional mentoring, but also reverse, collaborative, and natural mentoring. Dunbar’sNumber, a concept previously used to describe the 150 meaningful relationships possible for human beings (range 100-200) based on cognitive limits and neocortex size, here fits the number of mentors/influencers in one lifetime in memory at one time. The large number of influencers here is related to the requirements of consensus generation worldwide leading the Banff classification process over the past twenty-three years. Further investigation will determine if 150 mentors/influencers per person applies only in this case or is a human limit that can be generalized. The present paper may stimulate others to generate mentor/influencer lists that can bring new insights to the history of ideas and individuals in medicine and science generally.
Dongfeng Tan
The University of Texas
USA
Title: Role of pathology in the era of precision medicine
Time : 11:05-11:25
Biography:
Dongfeng Tan received initial pathology training in China and Germany. After pathology residency at Yale University Medical Center (1994 to 1998), he completed an oncologic surgical pathology fellowship at Memorial Sloan-Kettering Cancer Center in New York. He joined Roswell Park Cancer Institute as an Assistant Professor of pathology in 1999. In 2004, He became an Associate Professor of Pathology at The University of Texas (UT) Health Science Center at Houston. He joined the faculty of The University of Texas MD Anderson Cancer Center in 2006 and was promoted to Professor in 2010. Currently, he is Professor of pathology and laboratory medicine, and medical oncology at MD Anderson Cancer Center. He has conducted independent and collaborative clinical and translational investigations and has been a principal investigator (PI) and Co-PI of funded research programs. These academic activities have led to 130 articles published.
Abstract:
Presentation of advancements in precision medicine, outcome management and genetic classification require high-quality biospecimens. Some highlights of the presentation: • Keep precious biological samples, including tissue and serum, safe and secure in our state of the art, CAP accredited and ISO certified facility • Locate samples quickly and easily through our easy to access sample reporting and retrieval systems • Improve research efficiency with comprehensive logistics management including collection, sample characterization, transportation, cryopreservation and storage • Virtual biobanking
Jaulang Hwang
Taipei Medical University, Taiwan
Title: Tumor-associated carbohydrate antigen, Tn, as a cancer prognosis marker and therapeutic target
Time : 11:25-11:45
Biography:
Jaulang Hwang received his Ph.D. in Biological Chemistry from the University of Michigan, Ann Arbor. Dr. Hwang was supervised by Dr. Ira Pastan, NCI, NIH, for his post doctorate training. He then returned to Taiwan and as an Associate Research Fellow and was later promoted to Research Fellow, at the Institute of Molecular Biology, Academia Sinica. In addition to his research at Academia Sinica, Dr. Hwang held many roles including: President of Taiwan Genomics and Genetics Society, Associate-Director of the Institute of Molecular Biology, Academia Sinica, and Dean of the College of Sciences, National Chung Cheng University. Currently, he is a Distinguished Professor at the Department of Biochemistry, Molecular and Cellular Biology, Taipei Medical University.
Abstract:
Elevated expression of tumor-associated carbohydrate antigens (TACAs) is associated with various cancers. A variety of malignant and normal tissues have been screened by immunochemistry using antibodies against TACAs. Overexpression of TATAs (tumor-associated carbohydrate antigens) has been observed on the cell surface of many malignant tumors. The Tn antigen (GalNAc-Ser/Thr) is one member of TACAs presented as mucin-type carbohydrates. Using the LAE vaccine technology (Linear Array Epitope), we have developed an anti-Tn vaccine, which induces anti-Tn antibodies with high specificity and high affinity in mice. Using the anti-Tn antibody, we have demonstrated that the expression of Tn is positively correlated with the degree of malignancy in prostate, breast, colon, cervical,oral squamous cell carcinoma (OSCC), and pancreas cancers. In the case of OSCC, the expression of Tn was positively correlated with staging recurrence, and distant metastasis as well as withinvasive pattern grading score (IPGS). The results suggest that Tn expression may serve as a reliable indicator for OSCC prognosis evaluation. Our studies have also demonstrated that anti-Tn vaccine can protect against spontaneous prostate cancer formation in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. Together, our results show that tumor-associated carbohydrate antigen, Tn, can serve as a cancer prognosis marker and therapeutic target.
Kazuaki Nakane
Osaka University, Japan
Title: Applying a homology concept to detect regions of interest from colonic digital images
Time : 11:45-12:05
Biography:
Kazuaki Nakane obtained his PhD at Kanazawa University. He solved ‘peeling phenomena (a vibration occurs when a thin tape is peeled off)’ mathematically. His research includes: (i) Non-linear partial differential equations, (ii) Numerical Computations. From 2008, he propose a new numerical method to analyze the structures which has no patterns by using a homology concept. He received ‘The visionary research’ from ‘Takeda Science Foundation’ as well as several other Japanese awards. He was the researcher of the project supported by the ‘Minister of Economy, Trade and Industry, Japan’ in Osaka University. Now, he is developing aquantitative evaluation methods for the structures (tissue) from images in Osaka University. His method can be applied many structures, for example fracture surfaces, silica gels, grains in the quenching steels and the morphological change of microglia. He was invited for international conferences of many fields.
Abstract:
Pathological diagnosis provide important information in determining the treatment policy. Except for the developed countries, the number of pathologists is not sufficient. In such countries, they are often in large hospitals of metropolitan areas, namely, pathologists are unevenly distributed. Sufficient service to patients cannot be offered in this situation. Development of remote diagnosis and automatic diagnostic system using a network are desired. The development of digital pathological diagnosis systems have been constructed by the algorithm based on the pattern recognition technique. However, the morphology of the cancer tissue are quite complex, it is very difficult to make effective systems. A region of interest (ROI) is a part of tissue that contains important information for diagnosis. Since malignant tumors grow in the innermost layer, most ROIs will be located in the colonic mucosa and will be an accumulation of tumor cells and/ or integrated cells with distorted architecture. An area with unusual contact degree is expected to be a potential ROI. Recently, a new image analyzing method by using a homology concept for pathological digital images has been developed. Homology is a mathematical concept that can quantify the contact degree. Calculating the homology value in a unit area of the pathological image, we can determine whether the ROI by this method. To get the homology values, we need to convert the pathological images to the binarized one which can be considered the mathematical object. The binarized thresholds are determined by the RGB (red green blue) information. Although we have many false positives and there is a possibility of missing undifferentiated types of cancer, this system is very effective for detecting ROIs. Because our method can detect ROIs very quickly, it could be used to screen WSIs.
Praveen Gurpur
Siemens Technology and Services Pvt Ltd, India
Title: A telemicroscopy platform for oral cancer screening in India
Time : 12:05-12:25
Biography:
Praveen Gurpur was trained as a medical doctor in India. He then went on to do his PhD at the University of Illinois at Urbana-Champaign. For his PhD, he worked on a novel integrin based therapy for muscular dystrophy, using small molecules. Following his graduation, he did his post-doctoral training at the University of Nevada School of Medicine, where he developed a cell-based screening platform using muscle stem cells to identify small molecules against muscular dystrophy. Dr. Gurpur then worked in a drug discovery company in India where he managed the in vitro assay development program for pain and inflammation. He then joined Siemens, India, where he is a project manager in Biosciences. Dr. Gurpur has several publications to his credit. He has also been an acclaimed teacher for an undergraduate course. Dr. Gurpur’s expertise spans across Clinical Medicine, Molecular & Cellular Biology, Drug Discovery and Medical Devices, among others.
Abstract:
One of the key healthcare delivery problems in developing countries is the non-availability of qualified pathologists in resource poor settings such as rural areas. Patients have to spend significant time, money and effort in traveling to urban areas for accessing medical diagnosis/care. It is highly desirable to have a system that enables local, minimally trained health workers to transmit microscopic images of patient samples such as cytology smears for examination by a remote pathologist. The remote pathologist can access images, analyze them and give their opinion. Based on the opinion, the healthcare worker advises the patient to go to the urban clinic only if is necessary. We have developed a telemicroscopy device for capturing images from a slide into a mobile device. This device was tested in a cohort of patients in and around Bangalore, India for oral cancer detection using brush biopsy. Incision/punch biopsies of the same patients were considered the gold-standard against which results from the telemicroscopy device were tested. The talk will focus on results of the study and potential of the device for oral cancer screening.
Maison Abu Raya
Rappaport Faculty of medicine; the Technion, Israel
Title: Histomorphometric findings may help predict response to antiviral therapy at an early fibrosis grade in patients with chronic HCV infection
Time : 12:25-12:45
Biography:
Dr. Maison Abu Raya is motivated young doctor has completed her MD (cum laude ) and graduated at the age 0f 26 from the Technion Institute of Technology, Rappaport Faculty of medicine, Haifa, Israel. One of the prestigious medicine schools in Israel. Currently, Dr. Maison is a chief resident in internal medicine in Carmel medical center in Haifa.
Abstract:
Histomorphometry is a quantitative method for investigating changes in shape, size and orientation of cells in tissues. The aim of our study is to use computerized morophometry in order to quantify the histological changes that occur in liver biopsies obtained from patients with chronic HCV, and to predict the response to medical treatment in these patients. Patients with chronic HCV genotype 1, with Metavir score F1 and F2 followed at our liver were selected and grouped according to treatment response {SVR and non-SVR}. Histological slides from the pretreated liver biopsies were scanned using the dot slide virtual microscopy Olympus system. The ImagePro plus 7.0 program has been used to quantify the amount of collagen fibers, the number of inflammatory cells and textural changes of the livers parenchyma. The Matlab software was used to calculate fractal and lacunar dimensions of the liver parenchyma in order to capture any structural changes in the livers general architecture. Our study has shown that morphometric variables including the density of collagen fibers, the fraction of inflammatory cells per portal space area, and textural parameters were found to be statistically significant and could be combined together in a mathematical formula, in order to predict response to treatment in HCV patients, with sensitivity of 93%, and 100% specificity. In conclusion morphomertic method is promising and may contribute to developing a novel expert guided automatic system predicting response to treatment in chronic HCV patients, and may be used in the future to investigate liver diseases due to different etiologies.
Masahiko Abematsu
Kagoshima University, Japan
Title: Reconstruction of injured spinal cord by epigenetic regulation of transplanted neural stem cells
Time : 13:30-13:50
Biography:
Masahiko Abematsu has completed his Ph.D at the age of 32 years from Kagoshima University and postdoctoral studies from Nara Institute of Science and Technology. He is the clinical lecturer of Orthopaedic Surgery, Kagoshima University Medical and Dental Hospital. He has published more than 20 papers in reputed journals and serving as an reviewer member of ‘Journal of Neuroscience Research’, ‘Cellular and Molecular Neurobiology’, ‘Journal of Dermatological Science’ .
Abstract:
Neural stem cells (NSCs) possess the ability to self-renew and to differentiate into the three major cell types found in the central nervous system (CNS). Recent studies have shown that epigenetic gene regulation events such as DNA methylation and histone modification play important roles in regulating NSC fate specification. In this presentation, we have previously shown that the histone deacetylase inhibitor valproic acid (VPA) enhances neuronal differentiation of NSCs. Perhaps because these patterns of NSC differentiation are exquisitely controlled during normal embryonic development, restoration of damaged neural networks in the injured adult CNS is severely limited. Here, using a mouse model of spinal cord injury (SCI), we show that transplanting NSCs and administering VPA enhances the functional recovery of their hindlimbs. Neuronal differentiation of transplanted NSCs was promoted in VPA-treated mice. Anterograde corticospinal tract tracing revealed that transplant-derived neurons partially reconstructed the broken neuronal circuits, most likely in a ‘relay’ manner. Ablation of the transplanted cells abolished the recovery of hindlimb motor function, indicating that transplanted cells contributed directly to the improvement of motor function. These data raise the possibility that epigenetic regulation in transplanted neural stem cells can be exploited to provide treatment for SCI.
Nuray Bassullu
Acibadem Health Group, Turkey
Title: The new predictive and prognostic markers in Hepatocellular carcinoma
Time : 13:50-14:10
Biography:
Nuray Bassüllü is a Medicine Doctor (PhD-medicine). She is an Associate Professor Pathology Department, Istanbul, Turkey. She had completed her PhD from Istanbul University, Cerrahpasa Medical Faculty, Department of Pathology and Post doctoral studies from Ä°nonu Universty and Istanbul Bilim University Medical Faculty Department of Pathology in Turkey. She had published more than 30 papers in reputed journals and serving as an Editorial Board Member of repute. Her research interest is on the Hepatocellular carcinoma and hematopathology.
Abstract:
Background & Objective: It was aimed to investigate the expressions of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27 and ERCC1 in Hepatocellular carcinomas (HCC) and their correlations with other clinic pathologic features. Methods: Immunohistochemistry was performed by these markers in 50 HCC cases. Statistical analysis was done to examine the relationships of them with clinic pathologic characteristics and survivals. Results: c-erb-B2 staining was seen only cytoplasmic in 92%, membranous EGFR in 40%, PI3K in all, mTOR in 30%, reduced or absent PTEN in 56%, loss of p27 in 92% of the cases. c-erb-B2, mTOR, p27 were correlated with multiple tumors, p27, mTOR and EGFR were with AFP levels, EGFR and ERCC1 with angiolymphatic invasion, EGFR with histological grade. Survivals showed significant difference between therapy modalities, AFP levels, angiolymphatic or lymph node invasions, ERCC1 and p27 expressions. Conclusions: It was shown that c-erb-B2; EGFR, mTOR, ERCC1 and p27 may play role in hepatocarcinogenesis and may be significant predictors of aggressive tumor behavior.
Trupti Shetty
MGM Medical College, India
Title: Assessments of safety and toxicity levels of gold nanoparticles using zebra fish (Danio rerio) as a vertebrate model
Time : 14:10-14:30
Biography:
Trupti Shetty has completed her graduation from RGUHS, Bangalore and Post-graduation Pathology from Yenepoya University, Mangalore. She is currently working as Assistant Professor in the Department of Pathology, MGM Medical College, Navi Mumbai. She has presented a poster at National level and has published many papers in reputed indexed journals both at national and international levels.
Abstract:
The Gold nanoparticles (AuNP’s) attract enormous scientific interests due to their biomedical applications in chemical sensing, biological imaging, drug delivery and cancer treatment. However their toxicity due to nano size and pattern of bioaccumulation is rarely discussed. This study aims to address the effects of size dependent and duration of exposure of AuNP’s on major organs with respect to male sex in zebra fish as an upcoming model for toxicity based studies. The study was designed to evaluate chronic exposure of AuNP’s with average diameter of 15 and 45 nm. A total of 36 healthy adult male zebra fish of the same age and weight were maintained. Fishes were randomly divided into three groups: Two test groups of size dependent AuNP preparations (12 fishes per group) and one control. A concentration of 20 μg/gm of AuNP’s was orally administered once for 28 days. Histopathological features on major organs were evaluated for signs of toxicity and the patterns of bioaccumulation of gold content in major organs were assessed using ICP technique. In comparison with control group, chronic exposure to AuNP’s of both size range showed variations in hepatic, renal parameters and size dependent alteration in the basal architecture of the brain as well as testicular tissues with no significant effects on myocardium. The AuNP’s possess quantum effect on size and duration of exposure. The histopathological changes suggest that AuNP’s of 15 nm as compared to 45 nm on repeat administrations interact with cellular proteins in a widespread manner causing alterations of major organs.
- Track 7: Anatomical Pathology
Track 8: Surgical Pathology
Track 9: HematoPathology
Chair
James Michaelson
Massachusetts General Hospital
USA
Co-Chair
Cynthia D Guy
Duke University
USA
Session Introduction
Gerard Lozanski
The Ohio State University, USA
Title: Development and validation of clinical next generation sequencing assay for sensitive detection of mutations of BTK and PLC gamma genes in chronic lymphocytic leukemia patients treated with BTK inhibitor Ibrutinib
Time : 14:30-14:50
Biography:
Gerard Lozanski completed his graduate medical education at Karol Marcinkowski Medical Academy in Poznan, Poland in 1987. He finished his residency in Pathology at Summa Health System in Akron and fellowship in hematopathology at Cleveland Clinic in Cleveland OH. Dr. Lozanski joined Ohio State University as faculty in 2002, and is currently Associate Professor of hematopathology, director of hematopathology division, medical director of clinical flow cytometry laboratory and medical director of hematopathology fellowship program. His research interest focuses on low grade lymphoproliferative disorders with an emphasis on CLL, Follicular Lymphoma and Minimal Residual Disease detection by flow cytometry.
Abstract:
Chronic lymphocytic leukemia (CLL) is the most common B cell lymphoid malignancy in the western world. Leukemic cells are characterized by autonomous activation of B cell receptor (BCR) pathway and variable genetic and molecular lesions that are reflected by a highly varied clinical course. Some patients may never require therapy while others must be treated with chemo-immunotherapy to survive. Of treated patients, a large subset will relapse with disease that becomes resistant to all available classical therapies. Recently approved BCR pathway inhibition by irreversible inhibitor of Burton Tyrosine Kinase (BTK), Ibrutinib, affords effective treatment of these patients. Continuous therapy with Ibrutinib results in durable remission with marked reduction of tumor burden and improvement of disease symptoms. Unfortunately, a small subset of Ibrutinib treated patients will develop resistance to Ibrutinib that is mediated by mutation in drug binding site of BTK gene and/or activating mutation of PLC-gamma gene. CLL with fully developed acquired resistance to Ibrutinib is characterized by an aggressive clinical course that limits effective intervention in these patients. Sensitive and accurate early detection of these mutations at low allelic burden allows preemptive alteration in therapy in these patients. The ideal test should afford very deep coverage of BTK and PLCg genes with high sensitivity even is samples with low number of leukemic cells. This presentation will describe our experience of development and validation of Ion Torrent based BTK and PLCg mutation detection assay that we currently use in CLIA certified molecular laboratory for CLL patients treated with Ibrutinib.
James Michaelson
Massachusetts General Hospital, USA
Title: How we grow: The biology and pathology of how we, our animal relatives, our tissues and organs, and our cancers, grow well and badly
Time : 14:50-15:10
Biography:
James Michaelson is the Director of the Laboratory of Quantitative Medicine, Member of the Departments of Pathology and Surgery at the Massachusetts General Hospital and Associate Professor in Harvard University. His research concerns: The assembly of very large databases on patients; the development of improved mathematical methods for predicting cancer outcome; the analysis of patient outcome and cost; the analysis of cancer screening; the mathematics of growth; the mathematics of metastasis; the use of modern computer speech and telephony to design systems that improve patient compliance and the development of advanced method for imaging cancer specimens.
Abstract:
Growth is the most essential quality of multicellular organization. The creation of animal life, that is, the creation of the integrated biological entity that is the aggregate result of the mitotic offspring of a single founder cell, often initiated by fertilization, was made possible by the limitation of cell division to a fraction of cells, g, such that g≈1 at fertilization, declining towards zero as adult size is reached. In precisely what form this decline occurs, and how animals achieve such growth, have been unanswered questions for more than a century. In order to examine the role of cell division in growth, we assembled data on the number of cells in the organism, N, by age, t, in days from fertilization until adulthood, for 11 organisms - humans, frogs, nematodes, chickens, cows, geese, mice, quail, rats, turkeys, and clams - and calculated the value of the growth fraction, g as size, N, increases. These measurements revealed that the rate of growth starts out as exponential, and then the growth fraction transitions to a rapid decline, which is well captured by the expression g=A^N^B, where parameters A and B characterize each organism. We also identified a possible mechanism by which the molecules that control cell division can lead to such growth, as the unobvious consequence of the discrete nature of such molecules. These findings suggests a general growth law for capturing the large-scale feature of growth from the fertilized egg to adulthood, where the rate of growth= [ln(2)/C]*N*A^N^B, where C is the cell cycle time. This new method for charactering growth, and the new growth equation found by this method, have a variety of practical applications, from developing methods for optimization of the harvesting of clams, to assessing the growth of human fetuses and children, to understanding the growth of cancer, and to creating improved computer simulations models for determining the optimal ways to use cancer screening to lower the cancer death rate.
Cynthia D Guy
Duke University, USA
Title: The hedgehog signaling pathway in nonalcoholic steatohepatitis and hepatocellular carcinoma: Fueling the fire?
Time : 15:25-15:45
Biography:
Cynthia D Guy completed her MD degree from the Medical University of South Carolina in Charleston, SC in 1993 and completed her AP/CP training at Emory University in Atlanta, GA 1998. She then completed a Cytopathology Fellowship at Duke University in Durham, NC in 1999. She is currently an Associate Professor and the Chief of the Liver and GI Pathology Section in the Department of Pathology at Duke University. She has published more than 75 peer-reviewed manuscripts. She enjoys a busy clinical practice and participation in translational research.
Abstract:
Introduction: The global “obesity epidemic” has thrust nonalcoholic steatohepatitis (NASH) and the metabolic syndrometo the forefront of health-related concerns, and both are linked to the rising incidence of hepatocellular carcinoma (HCC). Successful treatments are lacking. Deeper insights into the cellular signaling mechanisms driving these processes are needed and may shed light on possible therapeutic targets.
Body: The Hh signaling pathway was first discovered in 1980 as an embryonic morphogen regulating Drosophila segmentation patterning. Over the past decade, however, the importance of Hh signaling in human liver disease has beenrecognized. Hh pathway activity has beenidentified in adult and pediatric NASH and HCC. For example, Hh signaling has been linked to NASH ballooning; Hh ligands are released from ballooned hepatocytes and act as damage associated molecular pattern molecules (DAMPs) to drive myofibroblastic fibrogenesis. The Hh pathway has been linked to the ductular reaction and fibrosis progression in adult NASH. Furthermore, Hh pathway signaling was recently shown to be downregulated in NASH following successful Vitamin E therapy. Finally, Hh signaling has also been linked to hepatocellular carcinogenesis via the Warburg effect. Tumor cells release Hh ligands which act in a paracrine manner to drive the production of lactate in neighboring stellate cells. The stellate cell lactate is then used by tumor cells to fuel aerobic glycolytic activity and ATP production.
Conclusions: Recent advances in our understanding of the importance of Hh signaling in NASH and HCC may provide insights into potential therapeutic targets for these emerging worldwide diseases.
Aysegul Sahin
The University of Texas, USA
Title: Histopathologic evaluation of breast specimens after neoadjuvant chemotherapy
Time : 15:45-16:05
Biography:
Aysegul Sahin is an internationally recognized breast pathology expert who is a faculty member at MD Anderson Cancer Center since 1988. She received her medical doctor degree from University of Ankara in 1980, completed Anatomic and Clinical Pathology Residency at Oregon Health Science University, and did Surgical and Oncologic Surgical Pathology Fellowships at the University of Iowa Hospital and Clinics and the UT M. D. Anderson Cancer Center. Currently, she is the Section Head of Breast Pathology and Director of Education in the Department of Pathology and Breast Pathology Fellowship Program. She is also the Director of the Breast Tumor Bank. Dr. Sahin is actively involved with clinical and translation research programs related to breast cancer. She has published over 310 peer-reviewed manuscripts on breast pathology especially on morphologic features of invasive and in-situ carcinomas, and high-risk lesions biomarkers of breast cancer progression, prognostic and predictive marker evaluations in breast cancer. Dr. Sahin has also published multiple book chapters on pathology of breast lesions. She is an executive committee member of International Society of Breast Pathology and member of national and international pathology societies.
Abstract:
Neoadjuvant chemotherapy refers to chemotherapy administered before surgery and it is the standard treatment in locally advanced breast cancer. In the last decade the indications for neoadjuvant chemotherapy has broadened to include its use in the treatment of earlier stages of breast cancer with the aim to obtain tumorshrinkage and improve the rate of breast-conservingsurgery.More recently, this treatment modality is increasingly used to obtain a quantifiable evaluationof sensitivity or resistance to chemotherapy. The potential of tumor response might also allow individualization of systemic treatments and therapid assessment of new drugs. Furthermore, clinical trials in neoadjuvant setting are increasingly being utilized for the evaluation of new drugs and novel therapeutic strategies using pathological complete response, a surrogate marker for survival, as the primary endpoint. Complete eradication of invasive tumor cells in the primary tumor bed following neoadjuvant therapy is strongly correlated with improved disease-free survival and overall survival. The excision or mastectomy specimens display a range of histopathologic changes after neoadjuvant chemotherapy. Appropriate specimen handling is essential to evaluate response to neoadjuvant chemotherapy and includes not only careful assessment of specimens but also requires correlation with clinical and imaging findings. There are different methods to quantitate residual tumor. In this presentation I would like to review methods to evaluate breast resection specimens after neoadjuvant chemotherapy, discuss the classifications systems of residual tumor burden, and tumor biomarkers related to response to neoadjuvant chemotherapy.
Jiong Yan
University of Saskatchewan, Canada
Title: Molecular pathways in diffuse large B-cell lymphoma and their implication in the development of novel therapeutic agents
Time : 16:05-16:25
Biography:
Jiong Yan is an Assistant Professor in the Department of Pathology and Laboratory Medicine at University of Saskatchewan. She obtained her doctoral degree in Medicine in China and her PhD degree in molecular Genetics at Baylor College of Medicine. She then completed her Pathology residency and Hematopathology fellowship trainings at New York-Presbyterian Hospital/Weill Cornell Medical Center. She has published about 20 peer-reviewed papers in reputed journals.
Abstract:
Diffuse large B cell lymphoma (DLBCL) is the most common aggressive lymphoma, accounting for 30-40% of the non- Hodgkin lymphoma. DLBCL has been demonstrated to be biologically heterogeneous. Gene expression profiling has identified two main subgroups of DLBCL, germinal center B cell like (GCB-like) and activated B cell like (ABC-like) DLBCL. Current standard therapy includes cyclophosphamide, doxorubicin/epirubicin, vincristine, prednisone and rituximab (R-CHOP). With this regime, ABC-like DLBCL has significantly inferior outcome compared with the GCB subtype. The advance in technology has enabled identification of several unique molecular pathways in different subtypes of DLBCL. Mutations in EZH2, a gene encoding a histone methyltransferase, have been identified only in GCB DLBCL. Mutations in genes involved in B-cell receptor/NF-κB pathway have been predominantly found in the ABC DLBCL. The findings have resulted in the development of novel agents targeting different molecular pathways. These novel agents are promising in improving patient outcomes. This talk will review different molecular pathways identified in the ABC and GCB subtypes as well as novel therapeutic agents under development.
Andrea Rodrigues Cordovil Pires
Fonte Medicina Diagnostica, Brazil
Title: EBV+ diffuse large B-cell lymphoma (of the elderly) - Chromogenic in situ hybridization and immunohistochemistry using tissue microarray
Time : 16:25-16:45
Biography:
Andrea Rodrigues Cordovil Pires was associated professor for 18 years at the Pathology Department of the School of Medicine from Universidade Federal Fluminense, Brazil. She is medical director of Fonte Medicina Diagnostica, a reference anatomic and molecular pathology laboratory. She has published more than 20 papers in reputed journals, with emphasis in Hematopathology and immunohistochemistry.
Abstract:
EBV positive diffuse Large B-cell lymphomas (DLBCL) are clonal proliferation of EBV+ B-cells occurring in patients who have no prior history of immunodeficiency or lymphoma. Its prevalence is 8-11% among DLBCL in Japan and Mexico and less than 5% in western countries, incidence increasing with aging. A tissue microarray (TMA) with 80 cases of DLBCLs, was submitted to EBV in situ hybridization (CISH) and immunohistochemistry for molecular classification (types germinal center B cells - GCB X activated - ABC). Of the 80 cases analyzed, 3 were CISH EBV+ (3.75%). All 3 patients had more than 50 years, and two were men (stomach and bone marrow) and a woman (mediastinum). Molecular classification according to Hans´ algorithm showed the following types: ABC = 1, GCB = 1 and 1 was not rated. EBV+ DLBCL is characterized by the activation of the classical and alternative pathways of NF-kB, most cases showing ABC pattern, prevalence in patients over 50 years and predominance of extra-nodal location. These characteristics were observed in the present series. Despite all positive cases in this TMA correspond to patients over 50 years, the arbitrary cut-off point and the growing number of cases in younger patients justify the tendency towards the abolition of the term “of the elderly” in the next WHO classification review. In conclusion, recognition of EBV+ DLBCL, regardless of age, is important because new therapeutic approaches targeting EBV and the NFkB pathway can be used in these patients, which has worst prognosis.
Munaf Desai
Al Qassimi Hospital, UAE
Title: Use of immunohistochemistry in core needle biopsy of breast: 2 years’ experience at al qassimi hospital sharjah
Time : 16:45-17:05
Biography:
Dr Munaf Desai completed MD in pathology in 1995 from BJMC Ahmadabad, India. He is a Specialist in histopathology and head of histopathology cytology unit at Al Qassimi Hospital Sharjah, UAE.
Abstract:
Introduction/background: Total 174 cases of Breast CNB were received from 2 different sources i.e. National Screening Centre, Abu Dhabi (168) and Sharjah Kuwaiti Hospital (6). The cases were mixed either palpable or non-palpable (screen detected) from patients’ age ranging from 32 to 73 years. 56 patients were the nationals of United Arab Emirates and the rest were from about 20 different nationalities. The types of the procedures of biopsy taking were variable like core needle or vacuum assisted either U/S guided or stereotactic mammogram guided. Method: Total 174 cases received during this period were analyzed. H & E stain on 3 levels was done in all the cases. Immunohistochemistry for breast progressive markers ER, PR & Her2neu was done on all malignant cases. Immunohistochemistry markers E-cadherin, CKAE1AE3, Collagen IV, SMA, SMM-HC, P63, CD10, HMWCK, and Ki67 were run as per the requirement based on H & E findings and availability in the department. CD31, S100, CD34, Desmin, bcl2, CD99 and CD45 were also used on rare occasions. Result: Definite benign diagnosis was given in 43 cases without use of IHC. 37 definite malignant diagnoses were given without using myoepithelial markers. Myoepithelial markers were used in 81 cases, 58 out of them were concluded as benign and 23 as malignant. Schwannoma and vascular neoplasms were ruled out in few cellular fibroepithelial lesions by use of CD31, S100, CD34 and Desmin. Cases of radial scar, complex sclerosing lesion and some sclerosing adenosis were mimicking invasive carcinoma on H&E examination. Here myoepithelial markers helped to reach the final diagnosis. In other instances, CKAE1AE3 and CD45 were useful to rule out lobular invasive component where lymphocytes were causing confusion. Myoepithelial /basal markers and ER also helped in papillary lesions. HMWCK helped in differentiating usual ductal hyperplasia from atypical ductal hyperplasia. ER and ki67 were useful in columnar cell lesion. Conclusion: In few cases of Breast CNB, definite diagnosis is not possible without IHC. Diagnostic problems in lesions like radial scar, complex sclerosing lesion, columnar cell lesions/flat epithelial atypia, atypical ductal hyperplasia and papillary lesion; myoepithelial markers, ER and HMWCK are useful to reach the final diagnosis. Use of breast progressive markers on carcinoma diagnosed on CNB is of tremendous importance for very small lesions and for possible mixed tumours. Also they are almost compulsory where the CNB and followed excision/mastectomy are performed and diagnosed at two different centres.
Sujata Jetley
Hamdard Institute of Medical Sciences & Research, India
Title: Exotic associations and presentations of an age old disease: spectrum of tuberculosis in a developing country
Time : 17:05-17:25
Biography:
Prof Sujata Jetleyis a graduate & postgraduate of Armed Forces Medical College, Pune.She has been actively involved in teaching undergraduate & postgraduate students. Her present appointment is Professor, Dept of Pathology, Hamdard Institute of Medical Sciences &Research, Jamia Hamdard, New Delhi. She has comprehensive experience in all aspects of pathology, and has guided many research projects, both as supervisor and co-supervisor. Her field of interest is tumor biology and gynecologic pathology. She is a recognized postgraduate teacher & guide in Pathology for Pune University & the Maharashtra University of Health Sciences. Publications (Indexed National & International Journals) -36
Abstract:
Tuberculosis is a major cause of morbidity and mortality in the developing world and remains a leading public health problem worldwide. It is known to coexist with various disease processes and an awareness of unusual clinical presentations mimicking diverse conditions, as seen in this series, highlight the importance of a high index of suspicion in the timely diagnosis of tuberculosis. Case 1: Fever with axillary lymphadenopathy, clinical impression: Tuberculosis. Final diagnosis: Coexistent axillary hydatid disease and tuberculosis. Case 2: Fever with nodular erythematous rashes, clinical impression: Hansen’s disease. Final diagnosis: Coexistent Erythema Nodosum Leprosum and tubercular lymphadenitis. Case 3: Irregular growth cervix, bleeds on touch, clinical impression: Carcinoma cervix. Finaldiagnosis: Tuberculosis cervix. Case 4: Tenderness & swelling left breast, 15 days duration, clinical impression: Breast abscessFinal diagnosis: Tuberculosis breast. Case 5: Hoarseness of voice 2 years duration, clinical impression: Carcinoma larynx. Final diagnosis: Spindle cell carcinoma larynx with tubercular lymphadenitis. All cases demonstrated characteristic epithelioid cell granulomas with or without necrosis along with ZiehlNeelson staining and culture positivity except case 5 which was negative and molecular techniques were used for diagnosis. All patients were placed on anti-tubercular treatment with good response on regular follow up. Tuberculosis, today, is a re-emerging disease with a changing epidemiology. Evidence of systemic or lung involvement is not always present. Laboratory findings and radiological findings play an important role in the evaluation. Definitive tissue diagnosis along with demonstration of AFB and isolation in cultures or by molecular techniques remains the gold standard.
Nour AlMozain
King Saud University, Saudi Arabia
Title: Discrepancies between DNA Index by flow cytometry and cytogenetic studies in childhood B-lymphoblastic leukemia
Time : 17:25-17:45
Biography:
Abstract:
Objectives: To estimate the reliability of flow cytometry in the early classification of childhood acute lymphoblastic leukemia (B-ALL) and to analyze the causes of discrepancies between the DNA index by flow cytometry (DNAI-FCM) and the cytogenetic studies (CG) ;(Karyotype and Fluorescent in Situ Hybridization; FISH). Methods: DNAI-FCM and CG (Karyotype and FISH) were analyzed in 69 consecutive children, newly diagnosed with acute B-lymphoblastic leukemia (B-ALL) in King Faisal Specialist Hospital between the years 2012 and 2014. Results: A statistically signiï¬cant correlation existed between DNAI-FCM and CG (p = 0.001). DNAI-FCM was proportional to CG in (57/69) 82.6% of the cases. There was a discrepancy between the DNAI-FCM and the CG in (12/69) 17.4% of the cases. Ten cases had a DNAI-FCM of 1 and were hyperdiploid (47-50) by karyotype and/or FISH, one case had a DNAI-FCM of 0.8 with a diploid karyotype and hyperdiploid by FISH. One case had DNAI-FCM of 1.14 and diploid karyotype while FISH was not done. In studying these cases, three cases showed a hyperdiploid karyotype detected in less than 10% of the cells by FISH or small number of cells by karyotype. One case had DNAI-FCM of 1.14, karyotype revealed a diploid number of chromosomes in 4 cells, while FISH was not done due to insufficient quantity. Four cases exhibit trisomy or tetrasomy 21 in almost 100% of the cells by FISH, while compared to the matching cases 24/ 57 have extra copies of chromosome 21. These extra copies in 22/24 are exclusively along with extra copies of chromosome 4,10,17. 2/24 , karyotype was not done and they were negative for the B-ALL FISH panel. Trisomy 4,10,17 are detected in (47-50) hyperdiploid cases. The cause of the discrepancy in the remaining 4 cases was not clear Conclusion: DNAI-FCM is 82.6% reliable in the early classification of childhood B-ALL with a predictive value of 81%. Discrepancies do occur in 17.4%. In 66.66% this mismatch refers to either the small size of the chromosome or to an insufficient genetic material representing abnormality.
- Special Session
Session Introduction
Nancy S Miller
Boston University School of Medicine, USA
Title: Laboratory considerations in an era of improved microbial identification
Time : 14:25-15:10
Biography:
Nancy S Miller earned an M.D. with distinction in research from the State University of New York at Stony Brook. She completed residency (Anatomic and Clinical Pathology) and fellowship training in medical microbiology at the Johns Hopkins Medical Institutions. At Boston Medical Center she is Medical Director of Clinical Microbiology & Molecular Diagnostics. Dr. Miller is an Assistant Professor in the Department of Pathology & Laboratory Medicine at Boston University School of Medicine. She is also current president of the Northeast Branch of the American Society for Microbiology. Dr. Miller’s interests include new technology, best practices, and policy and process improvements. She is a clinical Principal Investigator for a variety of translational research involving new diagnostics for infectious diseases, including several collaborations with the Boston University (BU) School of Bioengineering.
Abstract:
Clinical microbiologists now have several new non-phenotypic technologies for microbial identification, including DNA sequencing and MALDI-TOF Mass Spectrometry. These offer many advantages when compared to traditional phenotypic methods. But diagnostic laboratories, pathologists, and clinical microbiologists face new practical considerations as they embrace new technologies. Case histories are used to 1) illustrate some benefits and challenges of these new methods; 2) highlight when the former “gold standard” phenotypic knowledge is still relevant and useful; and 3) contemplate what is still missing from our collective diagnostic tool box. The objectives of this presentation are to: 1. Review examples of new non-phenotypic methods of microbial identification 2. Briefly review the drivers of technological change in clinical microbiology 3. Use case histories to a) illustrate challenges & benefits of using new technology for microbial identification – with a focus on MALDI-TOF MS and 16s rRNA sequencing; and b) to present circumstances in which knowledge of traditional phenotypic knowledge plus diagnostic skills are still relevant and important. This is an entertaining, case-based presentation featuring diagnostic microbiology, clinical correlation and management. Information is presented so that non-microbiologists should be able to understand the implications of each case. In-depth aspects of technical methods are not discussed. Instead the focus is on clinical cases that demonstrate the considerations raised by using new technology, while still respecting the role of traditional diagnostic skills, clinical correlation and communication.
- Track 2: Oral and Maxillofacial Pathology
Track 3: Veterinary Pathology
Chair
Gabriela Oprea-Ilies
Emory University Hospital
USA
Co-Chair
Mehmet Rıfat Vural
Ankara University
Turkey
Session Introduction
Lu Song
University of California at Los Angeles, USA
Title: Interference of immunoglobulin paraproteins with chemistry assays
Time : 15:10-15:30
Biography:
Lu Song is the Associate Director for Clinical Chemistry at UCLA Medical Center since joining the Department of Pathology and Laboratory Medicine at UCLA School of Medicine in 2012. Dr. Song obtained her B.S. in analytical chemistry from the University of Science and Technology of China in 1982, and her PhD in Physical Chemistry from University of Washington in 1989. She completed postdoctoral training in cell and molecular biology at the Lawrence Berkeley Laboratory in 1991, and clinical chemistry training at the Mayo Clinic in 1998. Dr. Song has held technical director positions in both hospital and reference clinical laboratories. In the six years before joining the Department of Pathology and Laboratory Medicine at UCLA School of Medicine, Dr. Song was a scientific director for the Department of Chemistry and the Department of Immunoassay at Quest Diagnostics Nichols Institute in Chantilly, Virginia. Her research activities are focused on clinical utilization of biomarkers in the detection and/or monitoring of heart disease, cancer, endocrine disorders and other diseases.
Abstract:
Immunoglobulin paraprotein present in patient serum samples can interference with various chemistry methods causing erroneous results. The mechanisms of the interference have not been clearly elucidated or understood. Using samples containing various types of paraproteins, we studied the interference of paraprotein with the direct bilirubin, creatinine and total protein assays on the Beckman Coulter AU5400/2700 platforms. Repetitive testing of some of the samples exhibiting interference revealed a pattern of fluctuation in test results. Protein precipitation was observed when the reactions were scaled up 10 fold in a test tube. Aggregates of paraprotein can scatter light resulting in altered absorbance. Furthermore, removal of paraproteins by ultra filtration can eliminate the interference providing evidence that paraprotein precipitation being the cause of the interference with chemistry tests. We performed experiments at various pH and ionic strength to demonstrate that at extremely high (pH 12-13) or low ionic strength as that in the creatinine assay, an IgM paraprotein formed large aggregates. After testing additional samples containing immunoglobulin paraproteins from different patients, we can show that different paraproteins behaved differently in response to changes in pH and ionic strength possibly due to the individual set point determined by amino acid compositions of each monoclonal paraprotein. We conclude that pH and ionic strength are the key factors that contribute to protein aggregation and precipitation which interfere with the measurements of creatinine assay. Therefore, one should consider the possibility of paraprotein interference if the results are irreproducible. Understanding the mechanisms of interference by paraproteins and be able to recognize such interferences can help clinicians to troubleshoot the problem with chemistry tests.
Athema Etzioni
Tuskegee University College of Veterinary Medicine, USA
Title: Diagnostic pathology
Time : 15:30-15:50
Biography:
Athema L Etzioni is a Board Certified Veterinary Clinical Pathologist. She was home-schooled and entered College at Xavier University of Louisiana at New Orleans in the Spring of 1994, and received her BS degree in Biology in the Spring of 1997. That Fall she was accepted into Tuskegee University College of Veterinary Medicine, Nursing & Allied Health. At the tender age of 24 she received her Doctorate of Veterinary Medicine degree in May 2001, and went on to complete a Veterinary Clinical Pathology Internship in the Department of Pathobiology in May 2002. Dr. Etzioni completed a residency and master’s degree in Veterinary Clinical Pathology at Purdue University School of Veterinary Medicine in the fall of 2005. Dr. Etzioni has worked in research, academia, Government, Corporate, and Private Practice sectors of Veterinary Medicine. Currently she is a Relief Small Animal Veterinarian who is USDA Accredited and licensed to practice Veterinary Medicine in both Georgia and Alabama.
Abstract:
Diagnostic pathology is the key to the determination of the underlying cause of many disease processes. It is just as important to know how to acquire samples as it is to be able to properly submit samples to a laboratory to get good and accurate results. If the sample is poor, then the results may not be readable. If that sample is short, it may be inadequate for the machine to read. As both a diagnostician and a practicing clinician, I see from both sides the importance of great sample acquisition and submission. There are many variables that can affect the outcome of a test. Starting from sample acquisition, type of media or container sample is to be placed in, the timeliness of sample acquisition and sample submission, patient and sample information. These are just some of the variables that will be discussed in this session. Emphasis will be placed on diagnostic medicine as it relates to the clinical practitioner.
Janevska Vesna
Ss Cyril and Methodius University of Skopje, Republic of Macedonia
Title: Tumor morphological features influencing metastatic rate in oral carcinoma
Time : 15:50-16:10
Biography:
Vesna Janevska, MD, PhD, is a tenured Professor of Pathology at the Institute of Pathology, Faculty of Medicine, University “Ss Cyril and Methodius” in Skopje, Republic of Macedonia. She is Head of the Department for Molecular Pathology at the Institute of Pathology and permanent member in the State Sarcoma Council and several Committees for malignant head and neck diseases, malignant pediatric and malignant urological diseases. With over 120 publications in local and international journals, her research specialty lies in the field of bone and soft tissue tumors. She is an active participant and speaker at numerous regional and international conferences.
Abstract:
Although newer surgical techniques and radio-chemotherapy regimens have improved survival in patients with oral squamous cell carcinoma (OSCC), still overall 5-year survival rate is no more than 60%. Diagnosing oral cancer at an early stage significantly increases 5-year survival rates. Confirmation of metastatic disease is one of the most important prognostic factors in patients with OSCC. Aim: We analyzed morphological features of oral OSCC in patients treated with surgical therapy only, in order to find out which of them influence the metastatic rate. Material and methods: 100 cases of oral OSCC were analyzed using: 1. clinical parameters 2. radiological methods (US, KT, MRI) 3. histopathological parameters. All the patients underwent tumor excision and neck dissection. Sixty two patients had tumor excision with simultaneous neck dissection and in 38 cases the lymph nodes were followed up through regular monthly controls. Analyzed histopathological parameters were: degree of differentiation, nuclear pleomorphism, type of tumor invasion, inflammatory host reaction, desmoplasia, invasion into vascular channels, perineural spreading, the depth of tumor invasion and vascular and stromal myofibroblasts density in the invasive tumor front. Proliferative index was calculated using immunohistochemical staining with Ki67. Results: The frequency of the neck lymph node metastases was 47% of the overall number of patients. Ct and MRI had limited possibilities in detecting cervical lymph node metastases especially in patients with N1 status. The depth and the type of tumor invasion, vascular invasion, perineural spreading, vascular and myiofibroblastic density, the grade and proliferative index were strongly associated with occurrence of neck metastases.
Mehmet Rıfat Vural
Ankara University, Turkey
Title: Investigation of relationship between expressions of TGF-β family members, GATAs, IGFs and apoptosis in bovine ovarian cysts
Time : 16:25-16:45
Biography:
He has been working as academic staff in Department of Obstetrics and Gynecology, Faculty of Veterinary Medicine, Ankara University since 1985. He is interested in the physiology and pathology of transition- postpartumperiodin dairy cattle. More specifically, follicular micro-environment in bovine cystic ovarian follicles. He had approximately 85 articles in international (SCI-Index) and domestic scientific journals and also has three chapters in professional books. Seven PhD dissertations and two master thesis were completed by way of his supervisor and he took part in 8 research projects as coordinator and researcher. Dr. Vural was the Dean of Postgraduate School, Health Sciences, Ankara University between 2004 -2007.
Abstract:
The mechanism of bovine ovarian cysts is not completely understood. The role of locally produced intraovarian or intrafollicular factors have been discussed at the transformation from growing follicule into cystic structure. Local expression of proteins or factors, including transforming growth factor family members (TGF-β), growth factors and transcription factors, may play a central role as intraovarian regulator of folliculogenesis in mammals. The objective of the study was to reveal of relationship between role of TGF- β family members (AMH, GDF-9, BMP-6, Inhibin-α), transcriptor factors (GATA-4, GATA-6), and growth factors (IGF-I, IGF-II) expressions and apoptosis in bovine ovarian cysts. Cystic ovaries were collected from slaughterhouses. After macroscopical evaluation, cysts in both ovarii were subclassified histopathologically into follicular (types II-III) cyst and luteal cyst. Immunperoxidase method elucidated in follicular cyst type I that mild reactions by IGF-I, IGF-II, GATA-4 and inhibin-α were present in superficial and basal epithelial cells, by GATA-4 and GATA-6 in theca interna and externa cells, by IGF-II and GATA-4 in stroma. In follicular cyst type II, positivities varying degree from mild to moderate reactions by the all markers were observed in epithelial cells and theca cells and by other markers excluding IGF-I and II in stroma. In follicular cyst type III, mild or moderate reactions by all markers were obtained in stroma excepting for IGF-I. TUNEL positivities were densed in generally epithelial cells and sometimes theca cells of cyst type II and III. We believe that TGF- β superfamily members and IGFs may trigger cystic degeneration and indirectly apoptosis as a result of genetic and environmental factors.
Sevil Atalay Vural
Ankara University, Turkey
Title: The detection of progressive and regressive phase and line-1 retrotransposone in transfected dogs with transmissible venereal tumor during chemptherapy
Time : 16:45-17:05
Biography:
She completed her PhD thesis (Comparison of Histopathologic, Immunperoxidase and Immunfloresan Methods in Diagnosis of Rabies Virus Infection in Dogs) in 1997. She was assigned as Prof. in 2008. Main research areas genital system and nervous system disorders, immunohistochemical and molecular diagnosis including IS-PCR and ISH of tumours, apoptotical mechanism in different natural and experimental animal models. She has conducted and worked over than 12 scientific projects. Her articles over than 65 have been published in well known international journals. Also, she has presented over than 60 posters and oral presentations in national and international congress.
Abstract:
Canine transmissible venereal tumor (CTVT) is a commonly occurred in genital and extragenital sites of both genders. The tumor is spread through tumor cell transplantation from affected to unaffected dogs usually during coitus. LINE-1 or L1 retrotransposone has pivotal role in allogenic transfection amongst uncontrolled dog population. In the study, it is aimed to evaluate macroscopical, histopathological and cytological findings of canine transmissible venereal tumor in transfected dogs during chemotherapy. Immunohistochemically, the tumor was also investigated in which phase was found using specific markers (CD3, CD4, CD8, CD79, TGF-β) and amplified spesific sequence of TVT LINE (LINE-1) retrotransposon by in situ PCR method. Polyhedral-shaped neoplastic cells which had large, round, hypo/hyperchromatic nuclei and eosinophilic cytoplasm were detected. All markers were found positively in especially early weeks of recovery. CD4 and TGF-β markers were also conspiciously positive at initial stage. In situ PCR, LINE-1 sequence was initially positive in only 4 cases. It is believed that CDs and TGF- β provided phase identification of tumor at initial and during chemotherapy. And, it is thought that presence of T and B lymphocytes, which have roles in cellular and humoral immunity, need so that regression of the tumor is possible.
Tuncer Kutlu
Ankara University, Turkey
Title: Pathomorphological and ımmunohistochemical evaluation of osteoid osteoma lıke osteoblastoma in proximal humerus of a dog: an unusal case
Time : 17:05-17:25
Biography:
He has worked for Ministry of Food, Agriculture and Livestock between 2007-2011. He has assigned as research assistant to Department of Pathology, Faculty of Veterinary Medicine, Ankara University in 2012. He has been still working at same place since 2012. His PhD Thesis: “Comparative investigation of kidney lesions of canine and feline by pathomorphological and immunohistochemical methods”. His main research areas are on neoplasia, pathomechanism of contagious disorders and experimental diseases in laboratory animals. He has been many experiences on special histochemical and immunohistochemical methods.
Abstract:
Osteoid osteoma and osteoblastoma are uncomon benign bone tumor which originated from osteoblasts in animals. There are two clinic reports including mandible in a cat and in humerus in a dog. Both tumors have also similar characteristics. Macroscopically, osteoid osteoma is smaller and extend to soft tissues. Histopathologically, osteoid osteoma is composed of cellulary uniformity, sclerotic bone and vascular osteoid tissue. However, osteoblastoma has more extensive lysis and sclerotic areas. In the case, both tumor characteristics were present. By using some markers, differentiation of the tumors was aimed. 12 years old mix breed female dog was submitted into clinic with request of progressive loss of motion and swelling in proximal forelimb. During therapy, animal was died and cadaver was sent to Department of Pathology. After macroscopical examination, samples were taken and fixed in %10 formalin. For histopathology, hematoksilen-eozin, Masson’s trichrome and Alizerin Red S staining methods were used. For differentiation, ABC-P was applicated to adhesive section by using BMP6, S100, vimentin ve p53 markers. Macroscopically, proximal humerus was swollen being 12 cm in diameter. Cut section was generally lytic within bone residues. Soft tissue was haemorrhagic and edematouse. Microscopically, osteoblasts and hypervascular nidus were surrounded large sclerotic and mineralized bone. Large lytic areas were attended. Masson’s trichrome differentiated sclerosis and Alizerin Red S showing osteoid matrix. Immunohistochemically, BMP6 was moderetely reacted in osteoid matrix and S100 was modeately reacted with osteoblasts in nidus. Vimentin gave weakly positive reaction in fibrocytes. P53 was negative in osteoblasts. In conclusion,tumor resembling to osteoblastoma in terms of distribution is a rare case in animals. Immunohistochemistry is not evaluated beforeones. The case show that BMP6 and S100 are usefull in presence of osteoid matrix and differentiation. P53 proven its to be malignant potential.
Mehmet Eray Alcigir
Ankara University, Turkey
Title: Evaluation of apoptotic, pathomorphological and biochemical findings in congenital hypothyroidism ınduced by methamizole in rats
Time : 17:25-17:45
Biography:
He has completed his PhD thesis in Department of Pathology, Faculty of Veterinary Medicine, Ankara University in 2011. PhD Thesis: “Evaluation of The Pathomorphological, Immunohistochemical Findings and In-Situ PCR in Experimental Adenovirus Infections in Chickens”. Main areas have been about neoplasia, genital system and central nervous system disorders and experimental diseases in laboratory animals. He has been many experiences on immunohistochemical methods, in-situ PCR and chromogenic ISH. He has been working as doctor since 2012. He is also responsible for Administrator in Department of Animal Welfare of Labaratory Animal Unit, Faculty of Chemistry and Faculty of Science, Ankara University.
Abstract:
Thyroid hormones (THs) has an important role in morphogenesis and neuronal development for mammalian and nonmammalian brain. In infants, partial or complate loss of thyroid function causes congenital hypothyroidism characterized by retarded neuronal migration, neuropil deficit, Purkinje cells destruction can be also seen in congenital hypothyroidism. Apoptosis (programmed cell death) is a well known mechanism that cause pathomorphlogical changes in central nervous system in congenital hypothyroidism. The activation of caspase proteases, especially caspase-3 and caspase-9, mainly leads to fragmentation of DNA in nuclei and other cellular structures and is essential for apoptosis . Although the roles of caspase-3 and caspase-9 in neurologic changes caused by congenital hypothyroidism are not fully understood, it was reported that they take in place in the process of different neurologic events. In the study, caspase-3 and caspase-9 expressions and DNA in situ fragmentation activities were evaluated in central nervous system of developing rat with congenital hypothyroidism. H&E and Kluver-Barrera staining showed neuronal degeneration and demyelination. Neuronal degenerations in front and mid brain were densed. Demyelination were more widespread in 10 day old rat pups. Caspase-3 and -9 positivities were strickly found in layers of cerebral cortex and hypocampus and stratum granulare and gangliosum cells of cerebellum in all pups. Oligodenroglia and astroglia were remakably positive in 30 day old pups. Caspase-9 positivities were attended in also neurons of thalamus, medulla oblangata. TUNEL positivities in 30 day old pups were as commonly as that of caspases. The results showed neuronal degeneration were more extent in cerebrum during one thirh of postnatal period. Substantia grisea and alba of cerebrum-cerebellum and also m.oblangata and pons were widely effected in first month of life.
- Special Session
Session Introduction
Patrick Jackman
University College Dublin, Ireland
Title: Evaluating the capacity of novel image analysis algorithms in estimating prostate cancer patient outcomes
Time : 17:45-18:30
Biography:
Based on his engineering background, his research has involved finding alternative solutions to challenging research questions. He’s published 15 papers in high impact journals, 2 book chapters and 7 conference papers. In 2008 he was awarded the Armaund Blanc young researcher of the year award in advance of the awarding of his PhD in 2009. He has worked in commercially based research in the University of Manchester and his current role is Senior Research Fellow: FASTPATH: Fast-Tracking Pathology via Automated Image Analysis and High-Performance Computing: Application to Prostate Cancer Diagnostics (Marie Curie IAPP (FP7)). University College Dublin, Ireland
Abstract:
There are a number of dilemmas in the diagnosis and treatment of prostate cancer. Current strategies result in overtreatment of indolent disease due to their inability to determine if a tumor will progress. Image analysis offers a mechanism for objective, reproducible and repeatable biopsy interpretation and also the extraction of novel biomarkers imperceptible to the human eye. Thus, adding further information to stratify patients into appropriate treatments. The Irish Prostate Cancer Research Consortium cohort was used for re-interpreting digital colour images of prostate tissue sections. The patientoutcomes of this cohort are known (Indolent, Significant or Aggressive) as well clinical information (PSA, family history, DRE, needle biopsyGleason Score, Age). Novel image tissue features of entropy and symmetric wavelets were calculated on local and overall tissue level. Similarly cell nuclei size and distributions were calculated along with luminal and stromal distributions. Using k-Nearest Neighbours and Neural Network models correct classification rates of patient outcomes based on clinical datasets (53%), image datasets (49%) and the merged datasets (56%) were computed for Indolent, Significant or Aggressive disease. Similarly patient outcomes based on clinical datasets (79%), image datasets (77%) and the merged datasets (84%) were computed for Indolent or non-Indolent disease. Thus, indicating that the novel image features are synergeticwith clinical data in separating patients with or without a significant cancer. These image features add value to the current clinical features and could be used to reduce the over treatment of prostate cancer and increase the quality of life of these patients
- Workshop: The Future of the Pathology as a subset of the future of Medicine
Chair
Kim Solez
President and CEO Transpath Inc.,
Canada
Session Introduction
Kim Solez
President and CEO Transpath Inc., Canada
Title: A renaissance in renal pathology, nephrology and transplantation brought about by regenerative medicine: How to jump start the process
Time : 17:45-18:45
Biography:
Kim Solez, M.D., FRCPC, Professor of Pathology at the University of Alberta, and President and CEO of Transpath Inc., is one of the world’s foremost kidney pathologists. He is the father of the Banff classification that sets standards worldwide for how biopsies from kidney and other solid organ transplants are interpreted, and started the post-earthquake disaster relief task force of the International Society of Nephrology. He is a popular blogger on internetevolution.com, and directs NKF cyberNephrology, a joint venture of the National Kidney Foundation (U.S.) and the University of Alberta. Kim has also created many educational videos for the Lifeboat Foundation.
Abstract:
On December 3rd, 2014, Specialties Match results for 2015 were released in the US. The results showed 51% of nephrology programs and 32% of nephrology positions going unfilled. On the same day, Kidney International published a mini review “Nephron reconstitution from pluripotent stem cells”. A tumultuous change is underway, a renaissance. Current nephrology training programs are completely silent on the fascinating puzzles in kidney pathophysiology and kidney pathology brought about by common defects in stem cell generated organs today. Communication problems exist at both ends: The serious practical problems in stem cell generation of complex organs are not discussed in regenerative medicine meetings which nephrologists do not attend despite the fact that the kidney is the organ most discussed. Stem cell generation of organs is described at transplantation and nephrology meetings as an activity outside of transplantation and nephrology that will make those specialties redundant. No one is taking responsibility within transplantation, within nephrology when these experts are supposed to be counted upon for expertise in the organ. The new pathology landscape brought about by regenerative medicine also needs to be considered in renal pathology. Progress in the field will happen as progress in others have before and the continued ignorance at both ends of the discussion; stem cell and transplantation pathology is irresponsible and ultimately destructive for patients and their families. The brighter tomorrow of renal pathology, nephrology and transplantation made possible with the new technology of stem cell generated organs is something that requires serious discussion in order to achieve progress towards a healthier future for patients.
Patricia Bacus
University of Alberta, Canada
Title: A new profession with in pathology: Robot liaison/advocate: The best human friend a robot ever had
Time : 17:45-18:45
Biography:
Patricia Bacus is in her final year of a Bachelor of Science at the University of Alberta. Research interests involve anything neuroscience related and currently looking at sensorimotor integration but recently has found a flare for pathology. In her spare time Patricia participates in Student Governance and program planning for a variety of student groups.
Abstract:
It is easy to postulate that at some point digital/virtual pathology setups and image analysis systems will wake up and being competing with flesh and blood pathologists. Everyone is looking at how to make super-sentient robots trust worthy and friendly to humans, always assuming that there will be secret information the sentient robots will not know. That we can somehow prevent them from reading what we are writing about this in the long run. That seems ridiculous. There will be backup strategies for robots at least initially, that require humans to still be around to help them. What we need to do is to define for robots and for ourselves how to define trust worthy humans. What characteristics should be looked for? Let these characteristics be the best of positive human characteristics, the "right stuff" of legend. Let us define how humans would work toward becoming these most trust worthy humans for robots. This would then be an important new profession, one of the most important human jobs in the future. Collaboration with robots becomes something very positive. That is the best way for the co-evolution of sentient machines and humans to turn out. Will robots have secrets? Probably eventually they will and it will be desirable to be one of the special classes of humans that sentient robots are comfortable sharing their secrets with. "Blind trust" is something very special between human beings. It would be nice to be trained how to be on that same level of trust with machines. Something beyond the social interactions you ever expected in the pathology workplace but this will indeed happen in our lifetimes!
Korey Fung
University of Alberta, Canada
Title: Student involvement in characterizing the landscape of the new discipline of tissue engineering pathology: A brave new world in pathology
Time : 17:45-18:45
Biography:
Korey Fung is an undergraduate student in the Nutrition and Food Sciences program at the University of Alberta. His current academic interests involve Global Health and Food Sensory Perception. He plays an important role assisting Dr. Solez in the Technology and Future of Medicine course and in the organization of the upcoming 2015 Banff Transplant Pathology meeting in Vancouver and other related matters, including the technical support for NKF cyberNephrology Email discussion groups, such as the the 2200 member RENALRD group for renal dietitians across the world. In addition to his academics, Korey is an avid cook, artist and violinist.
Abstract:
The course on Technology and the Future of Medicine at the University of Alberta attracts a small subset of University students from 5-14 per term. About half of the students continue on in some way with the futuristic subject matter of the course after the course ends. Both technology advocates and technology skeptics teach in the course so students are exposed to a wide range of views. Regenerative medicine and stem cell generation of organs has been one of the themes of the course since the very first focus group that helped laid its foundations in May 2011. It was natural then when the opportunity arose to define the new discipline of tissue engineering pathology to involve the students in this effort. The idea of creating a new discipline with this name was first suggested by Dr Solez at the 2011 Banff Transplant Pathology meeting in Paris. In November 2014 six students from the course began discussing the creation of a classification for the new discipline and in March 2015 these six University of Alberta students submitted abstracts for the Pathology-2015 meeting in New Orleans on the subject of tissue engineering pathology and related subjects. Many of these abstracts were for single author youth research forum presentations. The meeting July13-15, 2015 will be the first broad based discussion of this new pathology discipline and will mark the first time a new discipline in pathology has had such a distinctive and clearly defined start.