Day 1 :
Keynote Forum
Clay J Cockerell
Founder of Cockerell Dermatopathology, USA
Keynote: Dermatopathology diagnosis objectives
Time : 09:05-09:45
Biography:
Clay J. Cockerell, MD is Clinical Professor of Pathology and Dermatology at the University of Texas Southwestern Medical Center and Director of the Division of Dermatopathology. He is the President and Owner of Cockerell Dermatopathology and the past Medical Director of Cockerell and Associates Dermatopathology as well as a diplomat of the American Academy of Dermatology and American Board of Dermatopathology. Dr. Cockerell is internationally recognized for his contributions to both dermatology and dermatopathology. He is the past president of the American Academy of Dermatology. For many years, Dr. Cockerell has overseen an educational program designed to train the next generation of dermatopathologists. He has served as Associate Editor of the Journal of the American Academy of Dermatology and is on the editorial boards of a number of medical journals including the American Journal of Dermatopathology.
Abstract:
Learn how to integrate clinical information in making a diagnosis. Learn practical approaches to skin biopsies (including melanocytic lesions). Gain a working knowledge of special stains and immunofluorescence
Keynote Forum
Gene Herbek
President of College of American Pathologists
Keynote: The CAP and CAP accreditation overview
Time : 09:45-10:25
Biography:
Gene N Herbek is the College of American Pathologists (CAP) President and served as President-elect and Secretary-treasurer on the CAP Board of Governors. He also chaired the Finance Committee and Council on Membership and Public Affairs and served as Vice Chair of the Council of Scientific Affairs among others. He is the Medical Director of the Methodist Women’s Hospital laboratory and Medical Director of the Transfusion and Coagulation Services for the Pathology Center at Methodist Hospital both in Omaha and Nebraska. He is Board Certified in Anatomic and Clinical Pathology and graduated from the University of Nebraska Medical Center and Pathology Residency Training Program.
Abstract:
In this presentation Dr Gene Herbek will discuss the College of American Pathologists (CAP’s) mission and vision; pathologists’ critical role in patient care and the delivery of quality outcomes; the expertise and science behind CAP programs and services and the CAP’s efforts including the CAP’s leadership in laboratory accreditation to foster and advocate excellence in the practice of pathology and laboratory medicine worldwide. Dr. Gene Herbek will also share how the CAP partners with other domestic and international medical societies such as the American Society of Clinical Oncology (ASCO) and the International Association for the Study of Lung Cancer (IASLC) to develop evidence-based clinical practice guidelines to improve and standardize laboratory practices for better patient outcomes. The CAP strives to execute the Institute of Medicine’s standards for developing trustworthy clinical practice guidelines which includes conducting an open comment period prior to publication. All pathologists are encouraged to participate to ensure the recommendations are sound and reasonable. The CAP is committed to updating the guidelines as new evidence become available as is the case with the upcoming revision of Molecular Testing Guidelines for the Selection of Lung Cancer Patients which was developed in partnership with the Association for Molecular Pathology (AMP) and IASLC. To date, the CAP has published eight evidence-based guidelines and nine are currently in progress. Pathologists can take the lead by integrating these evidence-based guidelines into their practices according to their country’s regulations.
- 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.
- 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.
- 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.