Day 3 :
- Track 1: Molecular Pathology
Track 2: Hematopathology
Session Introduction
Jason X Cheng
University of Chicago, USA
Title: Identifying chromatin structures and the underlying novel mutations that predict therapeutic responses to epigenetic drugs in MDS and AML
Time : 10:45-11:10
Biography:
Jason X Cheng is an attending Hematopathologist at UCMC. He has obtained his MD and Master’s degree in China. He has received his PhD from the University of North Carolina-Chapel Hill. He has conducted the first genome-wide epigenetic profiling of DNA and histone (H3K27) methylations in MDS, which led to his winning the Pathologist-in-Training Award from the Society for Hematopathology and the Paul E. Strandjord Young Investigator Award from the Academy of Clinical Physicians and Scientists in 2008. He has published multiple papers in peer-reviewed, high-impact factor journals including Leukemia, PNAS, Immunity and Molecular Cell and received the Cancer Research Foundation Young Investigator Award in 2014.
Abstract:
Drugs targeting epigenetic-modifiers have been shown to be effective in a small portion of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), but the mechanisms underlying the efficacy of different epigenetic therapies are unknown. In this study, we performed growth-inhibition experiments with several epigenetic modifying drugs in multiple myeloid leukemia cell lines and identified two distinct lineage/differentiation-associated growth- inhibition patterns. We developed a new method, crosslink-assisted DNA modification immunoprecipitation assay (CDMIA), to simultaneously measure 5-methylcytosine (5-mC) and hydroxymethylcytosine (5-hmC). CDMIAs revealed significantly drug-responsive changes in 5- mC/5-hmC at the promoters of differentiation/lineage-controlling genes such as PU.1/SPI1. Immunoprecipitation experiments demonstrated lineage-specific, drug-sensitive interactions between the PU.1/SPI1 and GATA1 transcription factors and the DNA/histone modifying complexes. Sequential-ChIP and chromatin conformation capture (3C) showed that distinct chromatin structures at the gene locus in a lineage-specific manner. Importantly, novel mutations in TET2, TET3, DNMT3L and PU.1/SP1 were revealed by genome-wide sequencing and confirmed by Sanger sequencing. These mutations correlated with the altered interactions between PU.1/SPI1 and the DNA/histone modifying complexes and predicted the responses to epigenetic modifying drugs. Examination of clinical specimens from patients with MDS confirmed the presence of distinct lineage/differentiation-specific chromatin structures These results demonstrate the importance of functional genomics in the pathogenesis of MDS and leukemia and may identify individual patients who may benefit from therapies with one epigenetic modifiers rather than another.
C Cameron Yin
University of Texas MD Anderson Cancer Center, USA
Title: Clinical applications of immunoglobulin expression in acute myeloid leukemia
Time : 11:10-11:35
Biography:
C Cameron Yin has received her MD from Beijing Medical University and her PhD from the University of Wisconsin-Madison. She is currently an Associate Professor in the Department of Hematopathology at the University of Texas MD Anderson Cancer Center. In addition to clinical responsibilities on the Leukemia, Lymphoma and Molecular Diagnostic services, she has been actively participating in multiple research projects in the molecular genetic abnormalities in leukemia and lymphoma, which has led to over 100 research papers and over 20 book chapters.
Abstract:
It has been assumed that immunoglobulin (Ig) can only be produced by B-cells and plasma cells. Recently, we have reported that Ig can be expressed by other types of cells such as epithelial cancer cells. In this study, we studied Ig expression in acute myeloid leukemia (AML). We found that Ig was expressed at a high frequency and level in AML cell lines and primary myeloblasts but not in monocytes or neutrophils from healthy controls, by RT-PCR, immunohistochemistry and flow cytometry. We further assessed rearrangements of IgG VHDJH transcripts and found that AML-IgG had restricted (AML cell lines) or biased (primary myeloblasts) V usage. Moreover, its gene rearrangements showed evidence of somatic hyper mutation. Anti-human IgG reduced cell viability and induced apoptosis in AML cell lines, whereas anti-human IgK increased cell migration and chemotaxis. Our findings suggest that AML-Ig may play a role in leukemogenesis and AML progression and it may serve as a useful molecular marker for monitoring minimal residual disease or designing target therapy.
Shaoying Li
University of Texas MD Anderson Cancer Center, USA
Title: MYC/BCL2 double hit lymphoma
Time : 11:35-12:00
Biography:
Shaoying Li has received her MD from Beijing Medical University. She is currently an Assistant Professor in the Department of Hematopathology at the University of Texas MD Anderson Cancer Center. She is board certified by the American Board of Pathology in Anatomic Pathology, Clinical Pathology and Hematology. In addition to clinical responsibilities on lymphoma, leukemia and flow cytometry services, she has been actively participating in multiple research projects in lymphoma and leukemia, which has led to over 30 research papers and multiple book chapters. She also serves as a Member of Editorial Boards and ad hoc Reviewer for multiple journals. Her major research interests include molecular cytogenetic risk stratification of DLBCL with a focus on double hit lymphoma and MYC/BCL2 double expresser lymphoma, clinicopathologic and molecular study of mantle cell lymphoma and molecular genetics aberrations in lymphoma and leukemia.
Abstract:
Double-hit lymphoma (DHL) has been defined by 2008 WHO as a B-cell lymphoma with MYC/8q24 rearrangement in combination with a translocation involving another gene such as BCL2 or BCL6. The most common form of DHL has translocations involving MYC and BCL2, also known as MYC/BCL2 DHL. In the past few years, numerous case series of MYC/BCL2 DHL have been reported in the literature. Most cases of MYC/BCL2 DHL morphologically resemble diffuse large B-cell lymphoma (DLBCL) or B-cell lymphoma, unclassifiable with features intermediate between DLBCL and Burkitt lymphoma. These tumors have a germinal center B-cell immunophenotype but an aggressive clinical course characterized by a high proliferation rate, advanced-stage disease, extranodal involvement, high International Prognostic Index score and high serum lactate dehydrogenase levels. All tumors have a complex karyotype. Despite a variety of therapeutic approaches that have been used to date, patients with DHL have a poor prognosis. Here we will discuss the clinicopathologic, immunophenotypic, cytogenetic and prognostic features of MYC/BCL2 DHL and some remaining issues.
Hui Chen
University of Texas MD Anderson Cancer Center, USA
Title: Analysis of pre-analytic factors affecting the success of next-generation sequencing of solid tumors
Time : 12:00-12:25
Biography:
Hui Chen has completed her MD from Peking Union Medical College, PhD from Colorado State University, Postdoctoral Research Fellowship from Johns Hopkins Medical School, Residency training from Dartmouth-Hitchcock Medical Center and Clinical Fellowship training from Memorial Sloan-Kettering Cancer Center. She is an Assistant Professor in Molecular Pathology and Breast Pathology at MD Anderson Cancer Center.
Abstract:
Clinical laboratories are rapidly implementing next-generation sequencing (NGS) tests for mutation analysis, however there are few guidelines regarding sample quality for successful results. We aimed to establish tissue quality parameters for successful NGS in solid tumors and to improve NGS performance. Using a 50-gene hotspot mutation panel we identified the major cause for unsuccessful NGS analysis being DNA <10 ng, which was associated with extremely small and low cellularity samples. High success rates were associated with resection procedures and biopsied tumor >10 mm2. Independent factors leading to lower NGS success were cellular tumor areas and decalcification procedures. Tumor type and paraffin block age did not affect success. We optimized workflow and showed improved NGS success rates with pronounced improvement among tiny samples and cytology samples. Identifying pre-analytical tissue factors allows us to improve NGS performance and to successfully test tumors obtained from minimally invasive procedures.
Gabriela Oprea-Ilies
Emory University School of Medicine, USA
Title: Worse overall survival in breast carcinoma expressing p16
Time : 12:25-12:50
Biography:
Gabriela Oprea-Ilies has completed her residency and fellowship in Pathology at the University of Minnesota and continued with a Cytopathology fellowship at Emory University Hospital, after which she remained on staff. She is the Director of the Immunohistochemistry Laboratory at Grady Memorial Hospital in Atlanta and the Medical Director of an independent Molecular Lab in Atlanta, Georgia. She has published more than 25 papers in reputed journals and serves as an Editorial Board Member and as reviewer of medical journals of repute.
Abstract:
Genetic alterations affecting p16 protein is well described in human malignancies suggesting that inactivation of this pathway may be necessary for carcinogenesis. We aimed to study p16 in BC by immunohistochemical (IHC) methods in a large series of hormone receptor (HR) positive and triple negative tumors (TNT) in relation with demographic, pathologic features, biomarkers and clinical outcome. Invasive mammary carcinomas (IMC) diagnosed during a 7-year period were reviewed. The IMC markers ER, PR, and Her-2 scored by the new CAP standards were included. The tumors were studied as Her-2 positive, TNT, and hormone receptor (HR) positive. Tissue microarrays (TMAs) were stained with p16. P16 positivity was correlated with demographic and pathologic data and clinical outcome. Of the 157 IMC studied 37.6% where HR+ and 57.3% TNT. The age at diagnosis varied from 24-90 years. P16 was overall positive in 52.2%. Of the 75 p16 positive in AA, 12 were HR+ and 87%TNT vs. Caucasians who were 20% HR+ and 80% TNT. 85% of TNT showed statically significant p16 expression (p<.001) and they were correlated with basal-like BC, large tumor and high grade (all<.001). On univariate analysis, p16 positivity had a statically significant positive correlation with African-American (AA) race, TNT, large tumor size, high histologic grade and CK14 and it was inversely correlated with p53.Overall survival (OS) was statistically significant worse in p16 BC (p=0.0027), in the non-TNT (p=0.05) and in AA patients (p=0.001). In conclusion, p16 may constitute a prognostic marker and patients with p16 positive tumors may benefit from a more aggressive therapy. P16 expression may differentiate breast carcinoma subtypes and explain the more aggressive nature of TNT. High frequency of p16 positivity in breast cancers of African-American women may indicate different tumor biology.
Rajyasree Emmadi
University of Illinois Hospital & Health Sciences System, USA
Title: Molecular tumor boards: An evolving practice of medicine
Time : 14:15-14:40
Biography:
Rajyasree Emmadi is a Diplomate of the American Board of Pathology in Anatomic & Clinical Pathology as well as in Molecular Genetic Pathology. She is an Associate Professor in the Department of Pathology at the University of Illinois at Chicago College of Medicine. She is also a Member of the Professional Relations Committee of the Association for Molecular Pathology and has participated in efforts to preserve the integrity of the practice of Laboratory Medicine.
Abstract:
With the debut of Next Generation Sequencing (NGS) in the CLIA labs, additional specialized information has now become available to the multidisciplinary groups involved in individual patient treatment planning and therapy with regards to oncology. Traditionally, these discussions took place in organ-specific Tumor Boards (such as Breast/GI/GU/Head & Neck, etc.). Many institutions have begun to conduct ‘Molecular’ Tumor Boards that allow for in-depth analysis of NGS data. This data allows unprecedented access to the actual biology of the tumor, permitting design of therapies targeting the achilles heel of each tumor, moving away from the practice of blanket toxic therapies. Discussions are focused on “actionable” mutations and specific targeted therapies, possibly through clinical trials. At our institution we have initiated a ‘Precision Medicine’ Tumor Board that goes through this process of NGS data analysis and treatment selection. This lecture will describe the function of the Molecular Tumor Board with actual case examples with a detailed walk-through of the tumor biology and how to match up with newer (clinical trial) treatment options. Some of the limitations that accompany this massive new data source will also be discussed.
Xuanming Shi
University of Texas Southwestern Medical Center, USA
Title: SMARCA4/Brg1 coordinates genetic and epigenetic networks underlying Shh type medulloblastoma development
Time : 14:40-15:05
Biography:
Xuanming Shi has completed his PhD in 2009 from the University of Rostock, Germany and Postdoctoral studies in 2014 from the University of Texas Southwestern Medical Center. He is an Instructor there after 5 years of Postdoctoral training. He has published papers in PNAS 2011, Nature Communications 2014 and Oncogenesis 2015 about Shh signaling and epigenetic mechanism in medulloblastoma development.
Abstract:
Recent large scale genomic studies have classified medulloblastoma into four subtypes: Wnt, Shh, Group 3 and Group 4. Each characterized by specific mutations and distinct epigenetic states. Previously we showed that a chromatin regulator SMARCA4/Brg1 is required for Gli-mediated transcription activation in sonic hedgehog (Shh) signaling. We report here that Brg1 controls a transcriptional program that specifically regulates Shh type medulloblastoma growth. Using a mouse model of Shh type medulloblastoma, we deleted Brg1 in pre-cancerous progenitors and primary or transplanted tumors. Brg1 deletion significantly inhibited tumor formation and progression. Genome wide expression analyses and binding experiments indicate that Brg1 specifically coordinates with key transcription factors including Gli1, Atoh1 and REST to regulate the expression of both oncogenes and tumor suppressors that are required for medulloblastoma identity and proliferation. Shh type medulloblastoma displays distinct H3K27me3 properties. We demonstrate that Brg1 modulates activities of H3K27me3 modifiers to regulate expression of medulloblastoma genes. Brg1 regulated pathways are conserved in human Shh type medulloblastoma and Brg1 are important for the growth of a human medulloblastoma cell line. Thus, Brg1 coordinates a genetic and epigenetic network that regulates the transcriptional program underlying Shh type medulloblastoma development.
Joachim Moecks
Biomcon GmbH, Germany
Title: ReadMax: A novel showcase approach for FISH biomarkers
Time : 15:05-15:30
Biography:
Joachim Moecks holds a PhD in Applied Mathematics from the University of Heidelberg, Germany. He has worked in various fields of Bioscience and Medicine with contributions in biomath and biostats. He has published more than 70 peer review papers with subject-matter or methodological emphasis. Presently he is a Science Head of Biomcon, focusing on biomath and biostats contribution for biomarkers in molecular pathology in collaboration with university pathology institutes and pharma companies.
Abstract:
The recently published study demonstrates that novel approaches can overcome hidden issues in widely accepted FISH scoring approaches. The study dealt with EGFR-scoring in NSCLC, where the established Colorado scoring was found to blur actual aberrance and failed as predictor in pivotal trials. ReadMax represents a ‘maximizing strategy’, where the reader strives for recording of most aberrant cells. The reading results underwent a systematic analysis to identify different types of aberrance and to evaluate their predictive power for treatment with erlotinib. It was a surprising finding that scorings of polysomy and not amplification were the winners in predictiveness. Other areas may share hidden issues HER2, MET in different cancer types tend to rely mainly on the ‘ratio’ as quantification which is hazardous scientifically, as the role of polysomial aberrance is disregarded and is hazardous moneywise, as biomarker developments are based only on a narrow slice of the available aberrance information not a wise bet. The results of the ReadMax study are sketched and the methodological novelties are illustrated. The extension of this methodology to other areas of FISH biomarkers is discussed and real data results are presented.
Jessica A Hemminger
The Ohio State University Wexner Medical Center, USA
Title: Unclassifiable high grade B-cell lymphomas with overlapping features
Time : 15:30-15:55
Biography:
Jessica Hemminger has received her Medical degree from The Ohio State University (OSU) College of Medicine. She has completed her Residency in Anatomical Pathology and Clinical Pathology, Hematopathology Fellowship and Clinical Traineeship in Renal Pathology at OSU Wexner Medical Center (OSUWMC). Her clinical and research interests are in the areas of hematopathology and renal pathology and she serves as the Director of the Immunohistochemistry Lab at OSUWMC.
Abstract:
The 2008 World Health Organization (WHO) classification of lymphomas include two gray zone categories: B-cell lymphoma, unclassifiable with features intermediate between diffuse large B-cell lymphoma (DLBCL) and classical Hodgkin lymphoma (CHL) (BCLU-DLBCL/CHL) and B-cell lymphoma, unclassifiable with features intermediate between DLBCL and Burkitt lymphoma (BL) (BCLU-DLBCL/BL). BCLU-DLBCL/CHL demonstrates overlapping clinical, morphologic and immunophenotypic features between DLBCL and CHL and are frequently referred to as gray zone lymphomas. Many of these lymphomas occur in the mediastinum and show features intermediate between CHL and the DLBCL subtype primary mediastinal large B-cell lymphoma (PMBL). However, non-mediastinal BCLU-DLBCL/CHL also occurs. Rare instances of composite lymphoma with CHL and PMBL as well as synchronous and metachronous cases are also recognized. Immunophenotypically, the B-cell program is usually preserved but is accompanied by expression of CHL markers. The optimal therapeutic approach has yet to be established; however, studies have suggested treatment regimens used for non-Hodgkin B-cell lymphomas are more effective. BCLU-DLBCL/BL has morphologic, immunophenotypic and molecular features that overlap between DLBCL and BL. High grade B-cell lymphomas that harbor translocations involving MYC and BCL2 and/or BCL6, so-called double-hit and triple-hit lymphomas are commonly classified as BCLU-DLBCL/BL. Similarly, high grade lymphomas with MYC and BCL2 overexpression, as determined by immunohistochemistry (double-expressor large B-cell lymphomas), are also frequently placed in this WHO category. BCLU-DLBCL/BL are typically aggressive lymphomas and many are resistant to current therapies.
Xi Wang
University of Rochester Medical Center, USA
Title: Understanding the heterogeneity of breast cancer: Referencing the normal breast luminal epithelium
Time : 16:10-16:35
Biography:
Dr. Wang current research interest is the use of immunohistochemical staining and molecular methods to identify tumor cell orgin and differentiation.
Abstract:
Breast cancer is a heterogenous group of diseases. Molecular sub-classification has divided it into 5 different subtypes (luminal A and B, Her2, basal like and triple-negative non-basal). Although this stratification has impacted on breast cancer treatments and outcomes, patient response to targeted therapy or chemotherapy remains highly unpredictable. Dissection of the normal epithelium is fundamental to understanding breast cancer heterogeneity. Terminal ductal lobular unit (TDLU) is the primary site where the breast carcinogenesis initiates. It consists of two types of cells: Luminal epithelium and myoepithelium. Even inside the luminal epithelium, different cell types are present. For instance, only approximately 10-20% of luminal cells express ER, while majority of the luminal cells are ER negative. We studied the expression of AR and ER in normal breast luminal cells and found that their distribution pattern is the same as what was revealed in invasive breast carcinomas indicating that ER/AR positive luminal cells may serve as the “cell of origin” of ER/AR positive tumors. These different types of luminal cells could subject to different genetic mutations which could further confound the inter-tumor heterogeneity. We found that Tocopherol-Associated Protein (TAP), a vitamin E binding protein was co-expressed with ER in normal/benign breast luminal cells but was down regulated in 46% of ER positive breast carcinomas. This down regulation was associated with poorer clinical outcome in ER positive breast cancer patients. Our study on p53 alteration in breasts of BRCA carriers and non-carriers revealed that p53 positive normal/benign cells were ER negative luminal cells. We hypothesis that these cells could serve as the “p53 signature” to predict future risk for a high grade breast carcinoma.
Joachim Moecks
Biomcon GmbH, Germany
Title: MET status in lung cancer: Searching in FISH for prevalent patterns of gene aberrance
Time : 16:35-17:00
Biography:
Joachim Moecks holds a PhD in Applied Mathematics from the University of Heidelberg, Germany. He has worked in various fields of Bioscience and Medicine with contributions in biomath and biostats. He has published more than 70 peer review papers with subject-matter or methodological emphasis. Presently he is a Science Head of Biomcon, focusing on biomath and biostats contribution for biomarkers in molecular pathology in collaboration with university pathology institutes and pharma companies.
Abstract:
MET is a promising drug-target in lung cancer therapy and the development of several MET inhibitors is presently under way. The study reported the interesting result that the prevalence of MET amplifications is similar in squamous and adenocarcinomas without or with EGFR or KRAS mutations which suggests that MET amplification in therapy-naive NSCLC occurs independent of the other classifications (histology, mutation). The study found for EGFR in NSCLC by advanced bio-mathematical methods aside of amplifications also other patterns of aberrance with predictive power for treatment with erlotinib. This suggests investigating with these refined methods also the patterns of MET aberrance in NSCLC, since so far only amplifications were considered for selecting of MET inhibitor therapy. A pilot investigation in MET stomach cancer for n=88 cases found aside of amplification, two other prevalent patterns of aberrance-the impact and meaning of which is unknown. Approximately n=200 cases of MET in NSCLC will be collected from clinical routine FISH assessments. Multivariate approaches as described in will be used to describe the prevalent patterns of MET aberrance in these patients and investigate their relationship to other demographic, histologic and clinical properties.
Leon P Bignold
University of Adelaide, Australia
Title: Principles of genomic explanations for the complex histopathologic features of tumors
Time : 17:00-17:25
Biography:
Dr Bignold graduated in Medicine from the University of Western Australia, and has post-graduate qualifications in internal medicine, experimental pathology, and diagnostic histopathology. From the 1980s, he has practiced and taught general and diagnostic histopathology at the University of Adelaide and the South Australian state government pathology service (SA Pathology, formerly Institute of Medical and Veterinary Science). Dr Bignold has written many articles on how genomic instability might explain the histopathological features of tumors, as well as related issues. In 2015, he published "Principles of Tumors: a Translational Approach to Foundations", Elsevier, Academic Press, Waltham, MA. With colleagues, he has also published a study of the origins of tumor pathology: "David Paul Hansemann: Contributions to Oncology" Birkhäuser, Basel, (2007) and a volume on the history of medicine: "Virchow's Eulogies" Birkhäuser, Basel, (2008). In 2006, he edited a volume “Cancer: cell structures, carcinogens and genomic instability”. (EXS vol 96, 2006). http://link.springer.com/book/10.1007/3-7643-7378-4/page/1;
Abstract:
1. The histopathologic features of tumors are complex, and have long been described in terms of loss of specialised activities ('de-differentiation") and abnormal cell-growth processes, especially "anaplasia" (1) and "neoplasia". The precise molecular genomic bases for these histopathologic complexities of tumors have been little discussed. This paper analyses the phenomenology of tumors using genetic concepts, especially of traits, linkage of traits, and variation. 2. The individual abnormalities / traits of tumor cells are mainly (i) Unceasing accumulation of cells. (ii) Variable deviations ('traits') in cellular morphology, especially specialised activities. (iii) Variable deviations in normal spatial arrangements of tumor cells to each other (abnormal architecture). (iv) Variable deviations in spatial relationships of tumor cells to non-tumor cells (compression, invasion). (v) Ability to grow in other tissues (metastasis). 3. The combinations of abnormalities exhibit (i) Regular specificity so that types can be readily distinguished. (ii) Variability from tumor type to tumor type; between cases of the same tumour type; and between different foci of the same tumor. (iii) Variability in incidence of progressions. (iv) Variability in the appearance of 'subtype' morphologies. (v) Variability in the incidence of progression. 4. Genomic explanations suggested are: (i) The combinations of traits may be due to 'large' genomic events affecting complex loci. (ii) The variabilities in most aspects of tumors may be explained by variable 'functional morphisms' of genes.
Shiyang Pan
The First Affiliated Hospital of Nanjing Medical University, China
Title: A novel tumor biomarker
Time : 17:25-17:50
Biography:
Shiyang Pan has studied lung cancer over 20 years, during which he has found novel biomarkers for NSCLC and authored more than 100 peer-reviewed reports. He is the Editor-In-Chief of Clinical Molecular Diagnostics which was published in the end of 2013 by People’s Medical Publishing House (PMPH) and he has served on the Editorial Board for the Chinese Journal of Laboratory Medicine. He is the Director of the Laboratory Medicine Department of Nanjing Medical University and the National Key Clinical Department of Laboratory Medicine. He is the Chairman of the Jiangsu Society of Laboratory Medicine and Member of the Standing Committee of Chinese Society of Laboratory Medicine, and he has served on Review Committees for the NSFC and Health Administration of China.
Abstract:
Monoclonal antibody (McAb) is the key tool for cancer immunodiagnosis and immunotherapy. In our previous study, a cell clone which kept secreting high titer IgG1-type McAb named NJ001 against human non-small cell lung cancer (NSCLC) cells was obtained. The antigen named SP70 of NSCLC specifically identified by NJ001 was proved to be a protein with the relative molecular mass (Mr) of 70 kDa in cytoplasm of the cancer cell and blood stream of cancer patients. IHC results indicated that NJ001 could positively react not only to NSCLC, but also to ovarian cancer, pancreatic cancer and breast cancer, negatively or weak positively react to human small-cell lung cancer (SCLC), pulmonary pseudo tumor and other epithelial tumors. In soft agar assay, the colony formation efficiency of lung adenocarcinoma in NJ001 groups decreased in a dose dependent manner compare to the control group. For the concentration of 100 μg per ml, 200 μg per ml and 400 μg per ml, the inhibition ratio of colony formation was 23.4%, 62.5% and 100% respectively. Meanwhile, NJ001 caused significant reduction in tumor volume and tumor weight compared to control mice in lung cancer xenograft model. The tumor growth inhibition rate of 200 μg, 400 μg and 800 μg NJ001 groups was 10.44%, 37.29% and 44.04%, respectively. NJ001 also led to obvious cytomorphological changes and induced the apoptosis of human lung adenocarcinoma cell line SPCA1 significantly. The newly developed NJ001 selectively reacted to NSCLC tumor cells and so on and exhibited anti-tumor activity both in vitro and in vivo. SP70 is of great value concerning immunodiagnostics and immunotherapy for the cancers with the most high morbidity and mortality in China and holds promise for further research regarding the mechanism underlying tumorigenesis.
Biography:
Maciej Zerkowski is an application scientist at PerkinElmer from past 4 years till date.
Abstract:
There has been a rapid grown in the field of tumor immunobiology in recent years as a result of recent successes in cancer immunotherapies and it is becoming clear that immune cells play many sometimes conflicting roles in the tumor microenvironment. However, obtaining phenotypic information about the various immune cells that play these roles in and around the tumor has been a challenge. Existing methods can either deliver phenotypic information on homogenous samples (e.g., flow cytometry or PCR) or morphologic information on single immunomarkers (standard IHC). We present here a methodology for delivering quantitative per-cell marker expression and phenotyping, analogous to that obtained from flow cytometry but from cells imaged in situ in FFPE tissue sections. This methodology combines the sequential multi-marker labeling of up to 6 antigens using antibodies all of the same species in a single section; automated multispectral imaging (MSI) to remove the typically problematic FFPE tissue auto fluorescence and correct cross-talk between fluorescent channels and an automated image analysis that can quantitate the per-cell marker expression, determine the cellular phenotype, count these cells separately in the tumor compartment and in the stroma and provide high-resolution images of their distributions. We present here several examples of this new methodology in breast, lung and head and neck cancers. Each application example will show 6-plex multiplexed staining, per-cell quantitation of each marker and multi-marker cellular phenotyping from multispectral images of standard clinical biopsy sections as well as methods to explore the spatial distributions of the phenotyped cells in and around the tumor
- Track 2: Hematopathology
Track 5: Gastrointestinal and Liver Pathology
Track 6: Oral and Maxillofacial Pathology
Session Introduction
Adrian M Padurean
NeoGenomics, USA
Title: Recommendations for collecting and processing good quality bone marrow specimens
Time : 10:55-11:20
Biography:
Adrian M Padurean is currently the Medical Director of the NeoGenomics Florida Laboratory. He has received his Medical degree from Institutul de Medicina in Timisora, Romania. He has conducted medical research in the field of Cardiovascular Biology at Massachusetts General Hospital/Harvard Medical School and Mount Sinai Medical Center, New York. Subsequently, he has also completed his Pathology Residency at Regions Hospital in St. Paul, Minnesota and Hematopathology Fellowship training at the University of Minnesota. He has earned MBA in Healthcare Administration from the Quinlan School of Business at Loyola University Chicago.
Abstract:
Morphology was the sole criterion for diagnosing hematolymphoid malignancies for about 60 years until the REAL classification added in 1994 immunophenotyping to morphology. In 2001 the WHO revolutionized the world of hematopathology by introducing cytogenetics establishing the current tripod of morphology, immunophenotpying and cytogenetics necessary to diagnose and manage patients suffering from hematolymphoid ailments. Despite the remarkable technological progress that provided us with all these ancillary studies, morphological evaluation remains the initial and most important criterion in diagnosing hematolymphoid malignancies. Furthermore, the premise for a good morphological evaluation rests on obtaining and processing high quality specimens. A good quality specimen is also necessary for obtaining accurate flow immunophenotyping, cytogenetic or molecular results. In 2008 the new WHO blue book introduced for the first time recommendations with regard to the minimum length of a bone marrow core biopsy (at least 1.5 cm in length). However, the authors shied away from stipulating guidelines for the other specimens that are usually collected at the time of a bone marrow biopsy (aspirates, touch imprints, specimens for ancillary studies). This presentation will try to put together different aspects of collecting and processing bone marrow biopsies and aspirations in hope that this information will help in obtaining high quality specimens.
Wenqing Cao
New York University School of Medicine, USA
Title: MACC1 and its Clinical Significance as a Biomarker and Therapeutic Target in Colon Cancer
Time : 11:20-11:45
Biography:
Wenqing Cao received her MD from Tongji Medical University. She subsequently completed a residency in Anatomic and Clinical Pathology at Northwestern Memorial Hospital, Northwestern University Feinberg School of Medicine, and a Gastrointestinal Pathology fellowship at the Mount Sinai Medical Center. She is currently Associate Professor at the New York UniversitySchool of Medicine/NYU Langone Medical Center. Since 1998, Dr. Cao has done extensive basic and clinical translational research in GI malignancies. Dr. Cao has published more than 28 papers in reputed journals and has been serving as editorial board members.
Abstract:
Colorectal cancer (CRC) is one of the most common malignancies worldwide. Among the leading causes of cancer-related death, CRC is the third in men and second in women in developed countries, and third in both men and women in developing countries. The five year survival is over 90% in patients with early stages of cancer, 65% in patients with regional lymph node metastasis, but only 10% for patients with distant metastasis. Approximate one third of CRC patients had distant metastasis at the time when cancer was diagnosed.To improve the CRC patient outcome, in past decades, extensive research have suggested promising/potential biomarkers for early diagnosing CRC and predicting its metastasis/prognosis. The metastasis-associated in colon cancer-1 (MACC1) gene was identiï¬ed by a genome-wide search for genes differentially expressed by analyzing normal tissues, primary tumors, and metastatic lesions in CRC. Further studies suggest that MACC1 functions as a transcriptional activator for proto-oncogene MET expression. MACC1 overexpression is associated with crucial steps of transition from adenoma to carcinoma and progression from low stage to high stage CRC.Overexpression of MACC1 in CRC is associated with distant metastasis and poor prognosis. In animal studies, downregulating MACC1 expression inhibit CRC growth and metastasis formation. Here, we discuss MACC1,a recently revealed potential biomarker for CRC diagnosis, prognoses, and a potential therapeutic target for anti-tumor and anti-metastasis intervention strategies.
Jiaqi Shi
University of Michigan, USA
Title: Intraductal papillary mucinous neoplasm (IPMN) versus intraductal tubulopapillary neoplasm (ITPN): How to differentiate these two entities?
Time : 11:45-12:10
Biography:
Jiaqi Shi has received her MD and PhD from the Hunan Medical University and Postdoctoral training from University of Arizona. She has completed her Pathology Residency and GasteroIntestinal Pathology Fellowship Training at University of Michigan (UM) in 2015. Currently, she is an Assistant Professor in the Department of Pathology at UM. Among her many awards, she has won the prestigious 2011 Benjamin Castleman Award from the United States and Canadian Academy of Pathology (USCAP). She has published more than 30 papers in reputed journals and has been serving as an Editorial Board Member of repute.
Abstract:
The differential diagnosis between an intraductal papillary mucinous neoplasm (IPMN) and intraductal tubulopapillary neoplasm (ITPN) can be difficult sometimes. IPMN is a mucinous cystic ductal neoplasm of the pancreas, whereas ITPN is mostly a solid intraductal neoplasm of the pancreas with no or minimum mucin. Therefore, gross examination and imaging is helpful to distinguish between these two entities. However, there is histologic overlap that could lead to erroneous diagnosis. Some of the histologic features in IPMN can resemble ITPN. Immunohistochemical stains of MUC5AC and MUC6 can also be helpful. Most of the IPMNs are positive for MUC5AC and negative for MUC6, with the exception of oncocytic type IPMN, while the opposite is true for ITPN. There are 4 subtypes of IPMN based on the epithelial cell lineage: Gastric, intestinal, pancreatobiliary and oncocytic types. Differentiating IPMN subtypes has clinical significance as they are associated with diverse prognosis. In the end, the most important question to address when evaluating IPMN or ITPN resection specimens is whether there is an invasive carcinoma component, because the prognosis is largely dependent on the answer of this question. A thorough examination of the lesion is desired to rule out an invasion.
Alan Y Martinez
The Metro Health System, USA
Title: Necrotizing infections of the oral and maxillofacial region: Diagnosis, management and outcomes
Time : 12:10-12:35
Biography:
Alan Y Martinez has completed his Dental degree in Honduras and his Oral and Maxillofacial Surgery Residency in Peru. He is currently In charge of the division of oral and maxillofacial surgery at the MetroHealth System a level 1 trauma center in Cleveland, OH. He has published 6 articles in English and Spanish in different oral and maxillofacial surgery topics and he is a Reviewer of several journals.
Abstract:
Necrotizing fasciitis (NF) is a rare soft tissue infection of the subcutaneous tissue and superficial fascia that results in rapidly progressive necrosis with secondary involvement of the skin and muscle and a high mortality. Cervicofacial NF (CNF) is an extremely rare entity, accounting for only 2.6-5 % of all NF. There are several different historical descriptions and references to NF dating back to Hippocrates in 500 B.C., who described diffuse non-healing wounds. Pouteau and Gillespie in 1783 and 1785 described malignant and gangrenous ulcers, respectively. In 1871 Joseph Jones, a confederate army surgeon during the U.S. civil war, was the first to accurately describe NF calling it a “hospital gangrene” (Jones, 1871). Meleney in 1924 described 20 cases of hemolytic streptococcal gangrene (Meleney, 1924). Wilson in 1952 coined the term necrotizing fasciitis (Wilson, 1952). Yet, there is very little information on presentation, management and outcome of patients with NF specifically involving the head and neck. NF is classified as one of three types based on microbiologic findings: Type-1 is a polymicrobic infection with a combination of anaerobic and aerobic bacteria, Type-2 is a monomicrobial infection mainly due to group A beta hemolytic streptococci (GAS) and less commonly other streptococci and staphylococci and type 3 is a mono microbial infection due to marine vibrios. The clinical manifestations of NF include: Swelling, redness, pain, fever, blebs, bullae and crepitus. CNF is most commonly a sequalae of odontogenic infection. Less commonly CNF may occur as a consequence of soft tissue trauma. It may rarely occur in the absence of a known inciting factor or a known portal of entry of bacteria as was true in one of our patients (case #1). The spontaneous occurrence of necrotizing fasciitis has been reported to account for up 20% of patients. Cervicofacial necrotizing fasciitis is a rare disease associated with a high morbidity and mortality. Early diagnosis and rapid aggressive radical surgical treatment are the main factors associated with reduced morbidity and mortality.
Izak B Dimenstein
Info-Genesis, USA
Title: Grossing principles and techniques in maxillofacial pathology
Time : 13:20-13:45
Biography:
Izak Dimenstein is graduated from Mechnikov Medical Academy in Leningrad, former USSR, in 1964 and completed his PhD program at the same institution in 1969. He has worked as a clinical and anatomical pathologist in Leningrad, USSR. Since 1995, he worked as a pathologists’ assistant and grossing technologist at Mount Sinai Chicago Hospital and Loyola University Chicago Medical Center developed a website entitled “Grossing Technology in Surgical Pathology” (www. grossing-technology.com) in 2002. He has retired from Loyola University Chicago Medical Center in 2008. Currently, his main area of interest is the summarization materials on grossing technology and bone grossing techniques.
Abstract:
Grossing maxillofacial pathology specimens is often challenging. It requires following certain principle and employment a variety of techniques to avoid wrong practices and increase the turnaround time. Although in the most cases the main diagnosis is known, the pathologist is required to evaluate the extend of the tumor and interrelationships between involved tissues. Based on extensive personal experience, the optimal sampling is in the fresh state because fixation makes tissue brittle and discolored that is an impediment to present bone and surrounding tissue relationship. Due to fragility or variety of most specimens’ configuration, the use of mechanical power saws is limited. The main technical requirement to get a representative section is the specimen immobilization, which involves employment of different kind of tools and contrivances. In our experience, hard-pressed packing cartons are optimal for secure immobilization. The author is advocating the “third hand immobilization” principle for precise or serial sections. Decalcification monitoring and embedding follow-up are additional requirements for high quality microscope slide for the pathologist’s reliable diagnosis.
Soliman Ouda
King Abdalaziz University, KSA
Title: Salivary stress biomarkers-Are they predictors of academic assessment exams stress?
Time : 13:45-14:10
Biography:
Suliman Ouda is a professor in the Department of Basic Oral and Clinical Sciences, Faculty of Dentistry in King Abdulaziz University.
Abstract:
Purpose: The present study was conducted on undergraduate dental students to asses and compares the levels of salivary stress biomarkers including cortisol, immulnoglobulin A and α-amylase enzyme during periods of academic assessments and non assessments and to relate these biomarkers to students' academic performance. Methods: Saliva samples were collected from undergraduate dental students; one before taking a final assessment exam and another during non assessment period. Salivary stress biomarkers concentrations were obtained using Enzyme Linked Immunosorbent Assay (ELISA). Results: The level of salivary stress biomarkers including s-cortisol, α-amylase and immulnoglobulin A significantly increased during periods of assessment exams as compared to non assessment (p=0,000, 0.001 and 0.003 consecutively). The study found a significant correlation between salivary α-amylase and academic performance especially among male students (p=0.008) and those in their final academic year (p=0.040). Conclusion: We conclude that the stress of academic assessment can markedly increase the level of salivary stress biomarkers. Students who show less academic performance generally depict higher levels of salivary α-amylase, especially male students and those in their final academic year.
Hexige Saiyin
Fudan University, China
Title: Are basal microvilli on the microvasculature of pancreatic ductal adenocarcinoma a tumor specific target for therapies?
Time : 14:10-14:35
Biography:
Hexige Saiyin has completed his MD from Shanghai Medical University and worked as a Lecture in Fudan University. He has completed his PhD study in the School of Life Science, Fudan University. He has also worked as a Visiting Assistant Professor in MD Anderson Cancer Center in Houston. He has discovered the "hairy" micro vessels which contain many basal cellular projections in PDAC, named the projection as "basal microvilli". He is an Assistant Professor in the School of life Sciences, Fudan University. He has published more than 50 papers in reputed journals.
Abstract:
Pancreatic ductal adenocarcinoma (PDAC) is a uniformly lethal malignancy with near 6 months median survival. It is a stroma-rich, vascular-poor and hypo-perfused tumor, which was considered to prevents efficient drug or nutrient delivery in tumor microenvironment. Paradoxically, the tumor cells have robust glucose uptake and rare necrosis, suggesting that the microvasculature has might adopted an alternative way for nutrient uptake and cellular trafficking. Using adapted thick tumor section immunostaining and three-dimensional (3D) construction imaging in human fresh tissue samples, we identified an undiscovered feature of the mature microvasculature in advanced PDAC tumors; long, hair-like projections on the basal surface of micro vessels that we refer to as ’basal microvilli’. Basal microvilli were also observed in intrahepatic cholangiocarcinoma (ICC) and metastatic pancreatic neuroendocrine tumor (panNET), but not in hepatocellular carcinoma, glioblastoma and renal clear cell carcinoma. Basal microvilli in PDAC are richer and denser than ICC and panNET. Functionally, these basal microvilli have an actin-rich cytoskeleton and endocytic and exocytic properties and contain glucose transporter-1 (GLUT-1)-positive vesicles. Clinically, as demonstrated by PET-CT, the tumor microvasculature with the longest and most abundant basal microvilli correlated with high glucose uptake of the PDAC tumor itself. In addition, these basal microvilli were found in regions of the tumor with low GLUT-1 expression, suggesting that their presence could be dependent upon the glucose concentration in the tumor milieu. Similar microvasculature features which contain glucose were also observed in a K-Ras-driven model of murine PDAC. Altogether, these basal microvilli mark a novel pathological feature of PDAC microvasculature and ICC and panNET. Because basal microvilli are pathological features with endo and exocytic properties, they may provide a non-conventional method for cellular trafficking in PDAC tumors.
Anshoo Agarwal
RAK Medical and Health Sciences University, UAE
Title: Cytomorphological spectrum of cysticercosis: A study of 72 cases
Biography:
Anshoo Agarwal is the Professor & Chairperson (Pathology), RAK medical College and Health sciences University. She published more than 100 publications in National and International journals. Her main research focus is on Immunopathology & medical education.
Abstract:
Introduction: Cysticercosis is a worldwide infection caused by larval stage of a cestode, Taenia solium. Worm infestation is acquired by ingestion of undercooked pork containing the cysticerci. Cysticercosis is a common disease in most developing countries. It has its greatest prevalence in Mexico, other areas of Latin America, India, China, Africa and Europe. Cysticerci may present as single or multiple painless swellings in any organ or tissue of the body. The most common sites in order of frequency are the subcutaneous tissue, brain, muscle, heart, liver, lungs and peritoneum. These are usually mistaken clinically for dermatofibroma, neurofibroma, sebaceous cyst, dermoid cyst and calcified lymph nodes. Biopsy is a gold standard for definitive diagnosis of any lesion but nowadays fine needle aspiration cytology (FNAC) in the diagnosis of various parasitic lesions is well documented. In the present study we report clinical profile and cytomorphologic spectrum of cysticercosis findings on fine needle aspirates from 72 cases diagnosed as cysticercosis. Material & Methods: Over the period of 6 years, 72 cases of cysticercosis were diagnosed in the Department of Pathology, BPKIHS, Nepal & Shrivalli Nursing Home, Thane West, Maharashtra, India. All the patients presented with swellings of different regions of the body. FNA was performed with 22 gauge needle and 10 ml disposable plastic syringe. Aspirated materials were smeared onto the glass slides. Two slides were fixed immediately in 95% ethyl alcohol and stained with Papanicolaou stain. Two air dried smears were stained with May-Grunwald-Giemsa stain. Cases which were biopsied were processed for histopathological examination, stained with hematoxylin and eosin. Results: 38 patients were males and 34 patients were females. The age ranged from 1.5 to 76 years with majority of the patients (76.38%) being younger than 40 years of age. Most frequently affected site was upper extremity (47.28%). In 7 cases (9.73%) lingual cysticercosis was diagnosed in our study. Involvement of breast was seen in 4 cases (5.56%) which is a rare presentation. Clinically (98.7%) cases presented with a solitary lesion in the present study. Fine needle aspirates in our study yielded clear fluid in (32.27%) cases, blood mixed aspirate in (23.01%) cases and pus like aspirate in (44.72%) cases. Fragments are bluish fibrillary glial like structure. Outer wall layer was seen thrown into rounded wavy folds with tiny ovoid nuclei in a fribrillary stroma comprising of thin reticulin fibrils beneath it. In rest two of the cases (2.77%) diagnosis was suggested on associated other cytomorphologic features and inflammatory reaction comprising of eosinophils, neutrophils, histiocytes, epithelioid cells, lymphocytes and giant cells in varying proportions which were confirmed later on biopsy. In our study 24 cases (33.33%) were misdiagnosed clinically as cases of dermatofibroma, neurofibroma and sebaceous cyst. Conclusion: FNA cytology is a simple and reliable procedure for the diagnosis of cysticercosis. In principle, a mass produced by cestode should not be diagnosed by FNAB since it might cause anaphylaxis and/or dissemination of parasites.
- Track 7: Digital Pathology and e-Pathology
Track 8: Anatomical Pathology
Track 9: Surgical Pathology
Session Introduction
Leon P Bignold
University of Adelaide, Australia
Title: The kinds of genomic events for the histopathologic complexities of tumors
Time : 14:35-15:00
Biography:
Dr Bignold graduated in Medicine from the University of Western Australia, and has post-graduate qualifications in internal medicine, experimental pathology, and diagnostic histopathology. From the 1980s, he has practiced and taught general and diagnostic histopathology at the University of Adelaide and the South Australian state government pathology service (SA Pathology, formerly Institute of Medical and Veterinary Science). Dr Bignold has written many articles on how genomic instability might explain the histopathological features of tumors, as well as related issues. In 2015, he published "Principles of Tumors: a Translational Approach to Foundations", Elsevier, Academic Press, Waltham, MA. With colleagues, he has also published a study of the origins of tumor pathology: "David Paul Hansemann: Contributions to Oncology" Birkhäuser, Basel, (2007) and a volume on the history of medicine: "Virchow's Eulogies" Birkhäuser, Basel, (2008). In 2006, he edited a volume “Cancer: cell structures, carcinogens and genomic instability”. (EXS vol 96, 2006). http://link.springer.com/book/10.1007/3-7643-7378-4/page/1;
Abstract:
1. Tumors are accepted to arise by way of somatic mutation / genomic event, but no particular mutation has been found in all tumors. Conventional (Mendelian) genetics may be able to account for combinations of traits by mutations of complex loci. The occurrence of tumors in different types could be explained by the existence of one or a small number of different tumorigenic-when-mutant complex loci for each tumor type (1). Variability in tumors may be explicable by variable functional morphisms / particular nucleotide alterations in genes in the complex loci. 2. The kinds of mutations (genomic events) which can affect complex loci are mainly (i) Oligonucleotide deletions or insertions causing frameshift mutations. (ii) Chromosomal-type errors, which are mainly deletions, amplifications, inversions and transpositions. These can be so large as to be visible in chromosomes by microscopy (hundreds of megabases), or so small that they can only be demonstrated by various probe-hybridization methods (tens of kilo bases). (iii) A lesion comprising dense clusters of nucleotide errors in lengths of DNA up to a replication 'bubble' (approximately 150kb) long (2). These focal replicative infidelity lesions are difficult to detect. 3. Variable functional morphisms could occur with any of these mechanisms of genomic events in complex loci. 4. These issues may be resolvable by new methods for high throughput nucleotide sequencing. (1) Bignold LP "Principles of Tumors", Elsevier Academic, 2015, chapters 1 and 8 and Appendix 2. (2) Bignold LP. Carcinogen-induced impairment of enzymes for replicative fidelity of DNA and the initiation of tumours. Carcinogenesis. 2004 25:299-307.
Biography:
Mark Priebe has presented numerous poster and podium presentations on Quality Assurance in Anatomic Pathology and he is a part of the speaker group for the Society for Improvement in Diagnostic Medicine. He is a Medical Technologist certified by the American Society of Clinical Pathology in both Medical Technology and Blood Banking. He is the Co-Inventor of the QualityStar external quality assurance program for anatomic pathology.
Abstract:
Every year, 1.6 million Americans are diagnosed with cancer. Getting the diagnosis right the first time is critical to designing the appropriate treatment plan and therapy. Pathology and radiology play significant roles in the diagnostic process. When things go wrong, 46% of the errors in diagnosis come from Pathology and Radiology, while 97% of the cancer diagnosis is based on the pathology specimen. Over the past 20 years, multiple studies have shown that the rate of major discrepancies identified for cancer patients referred to another institution range from 4.2-13.1% yet published data indicates the current intralab Quality Assurance (QA) ability to detect these discrepancies is only 0.8-1.7%. This clearly identifies a gap in our current quality practice and an opportunity to improve quality assurance initiatives. This abstract reviews the formal Quality Assurance programs and how they can be utilized to provide continuous quality improvement resulting in positive patient and institution outcomes.
Lorenzo Azzi
University of Insubria, Italy
Title: Burning Mouth Syndrome. What is new?
Time : 15:25-15:50
Biography:
Lorenzo Azzi is a PhD student of the “Biotechnology, Biosciences and Surgical Technology” course at University of Insubria. He is an oral surgeon and oral pathologist. He is assistant director of the Unit of Oral Pathology, Ospedale di Circolo Fondazione Macchi, Varese. He is active member of the Italian Society of Oral Pathology and Medicine (SIPMO) and of the European Association of Oral Medicine (EAOM)
Abstract:
Burning Mouth Syndrome (BMS) is regarded as a puzzling condition for clinicians coming from different specialties. Once considered as a psychiatric disorder, in recent years a new hypothesis for a possible role of the peripheral nerve fibers in the pathogenesis of the syndrome has been suggesteded. The purpose of this presentation is to shed light on the very often controversial data collected from the scientific literature and to illustrate the different important findings of the research carried out in our Institute, which could provide a great help to better understand this mysterious pathology. Salivary fluids analysis, topical application of different molecules, psychological anamnesis, epidemiological data, laboratory and histological findings are described. A following detailed diagnostic and therapeutic approach adopted in our trial is described, supported by the most recent findings in literature and in our research protocols.
Munaf Desai
Al Qassimi Hospital, UAE
Title: Histopathological features of granular cell tumor: A report of three cases
Biography:
Munaf Desai is MD in Pathology from BJMC in 1995, Ahmadabad, India. He is a Specialist of histopathology and currently is the Head of Histopathology Cytology Unit at Al Qassimi Hospital Sharjah, UAE.
Abstract:
Introduction: Granular cell tumor (GCT) is a rare soft tissue neoplasm of neural differentiation that can occur at any site of the body. The tumor is usually benign with rare incidence of malignancy. The diagnosis of GCT requires histopathologic examination of the excised lesion. We present three histopathology case reports of GCT tumors at three different sites in three different patients. Case Presentation: Case 1: An excision biopsy of a painless soft tissue mass at elbow of a 26 years old female patient received for histopathologic examination. Case 2: Completely removed tumor from the right fronto-parietal mass with dural attachment of a 73 years old female patient with clinical diagnosis of meningioma was received for histopathologic diagnosis. Case 3: A skin lesion on the chest wall of a 24 years old male patient was excised and sent for histopathologic examination. The clinical diagnosis was ‘Dermaoid Cyst’. Diagnosis of benign GCT was given in all of them after microscopic examination of routine Hematoxylin & Eosin stained sections, periodic Acid-Schiff (PAS) special stain and appropriate immunohistochemistry markers. Conclusion: GCT is a rare mostly benign tumor and rarely diagnosed prior to histopathologic examination of the excised specimen. Immunocytochemistry study and PAS special stain are needed to give confirm diagnosis of GCT.
Kazuaki Nakane
Osaka University, Japan
Title: Classification of degree of differentiation of colorectal neoplasm by the concept of the homology
Time : 16:30-16:55
Biography:
Kazuaki Nakane has obtained his PhD at Kanazawa University. He is a guest Associate Professor and a specially appointed Researcher in Osaka University. By using an idea of homology, he has developed a new image analysis method and applied this method to detect cancer lesion. He has also been successful in image analysis of complex images which seem to have mathematical structures.
Abstract:
Introduction: Recently, a new method based on the homology theory for analyzing histological digital images has been developed. The method evaluates the Betti numbers in a unit area of an image of a colon to determine the region of interest (ROI). The Betti number can be used to assess the degree of connectivity in tissue. Here, we change the binarizing threshold and investigate the relation between the change ratio of the Betti numbers and the different types of cancerous tissue. Materials & Method: Colonic specimens were provided by the Osaka Medical Center for Cancer and Cardiovascular Diseases. Data were gathered for internal quality control on a routine basis and all patients gave informed consent for data collection. Results: The calculated results can be approximated by quadratic functions. The distribution of the coefficient on the squared term and the x-coordinates of the vertices are shown. We can see a characteristic distribution for each type of cancerous tissue. Discussion: As the binarizing threshold decreases, the images gradually fade to white and the structure of the tissue is lost. Under the proposed procedure, in areas where the connections in the tissue are tight and clear, the one-dimensional Betti number changes slowly; conversely, where the connections are vague, such as in a background area filled with impurities, it changes very quickly. The state of this change can be considered an expression of the strength of the connectivity and it differs by type of cancerous tissue.
Hisataka Kitano
Nihon University, Japan
Title: An EGF motif of Del1 suppresses notch function and inhibits efficient angiogenesis in vivo
Biography:
Hisataka Kitano is an Assistant Professor in Nihon University of school of Medicine, Division of Oral surgery, Japan. He began a study of Del1 in 2005 in the present laboratory. He clarified deposition into extracellular matrix of Del1, apoptotic function, endocytosis function. He studied cancer gene therapy using Del1 in vivo. He treated the oral neoplasia as an oral and maxillofacial surgeon at a Nihon university school of medicine, Itabashi hospital.
Abstract:
Introduction: Del1, an ECM protein, is known to show pro-angiogenic or anti-angiogenic activities depending on the experimental conditions. It consists of two discoidin domains (C1, C2) and three epidermal growth factor (EGF) motifs (E1, E2, E3), of which E2 has been reported to contain an RGD sequence that binds to integrin receptors and supports endothelial cell survival. In the present study, we provide evidence that an E3C1 fragment suppresses Notch signaling and angiogenesis in explanted tumor model. Materials & Methods: Cells of the human oral squamous cell carcinoma cell line, SCCKN, were injected into nude mice to generate explanted tumors. cDNAs encoding, the E3 and C1 domains of Del1 (E3C1), were inserted into pcDNA3D (pE3C1) and injected into the tumors every 7 days with a transfection reagent, jet-PEI. Tumor angiogenesis was evaluated by immunohistochemistry with antibodies for PECAM, von Willebrand factor and PDGF-beta and intravenous injection of Lycopersicon esculentum lectin. The signal transduction of notch was analyzed by western blotting. Results: Treatment with pE3C1 suppressed the growth of explanted tumors and improved life prognosis of mice. In localization with immunostaining of PECAM or von Willebrand factor, and angioglaphy with Lycopersicon esculentum lectin, vasculature without lumen was increased by gene therapy of Del1 fragment. Among the treatment with pE3C1 and control, the PDGF beta staining cells, which is marker of tip cells in angiogenesis, were increased. Western blotting of human umbilical endothelial cells cultured with an E3C1 recombinant protein showed the decreased expression of active notch and hey1. Discussion: The phenotype of tumor vascular by treated with pE3C1 was analogous to the phenotype of inhibited of notch. In our study, it is suggested that the effective angiogenesis was inhibited by E3C1 inhibition of notch function. There is an anti-angiogenic domain, E3C1, adjacent to the RGD in E2 of Del1. The presence of domains with opposing activities next to one another in the same protein could account for the seemingly ambiguous characteristics of Del1 activity on angiogenesis. The EGF domain of Del1 has amino acid sequence, CXDXXXXYXCXC, which was shared by notch and delta. Signaling way of the motif should be investigated for notch function.
Hisataka Kitano
Nihon University, Japan
Title: An EGF motif of Del1 suppresses notch function and inhibits efficient angiogenesis in vivo
Time : 16:55-17:20
Biography:
Hisataka Kitano is an Assistant Professor in Nihon University of school of Medicine, Division of Oral surgery, Japan. He began a study of Del1 in 2005 in the present laboratory. He clarified deposition into extracellular matrix of Del1, apoptotic function, endocytosis function. He studied cancer gene therapy using Del1 in vivo. He treated the oral neoplasia as an oral and maxillofacial surgeon at a Nihon university school of medicine, Itabashi hospital.
Abstract:
Introduction: Del1, an ECM protein, is known to show pro-angiogenic or anti-angiogenic activities depending on the experimental conditions. It consists of two discoidin domains (C1, C2) and three epidermal growth factor (EGF) motifs (E1, E2, E3), of which E2 has been reported to contain an RGD sequence that binds to integrin receptors and supports endothelial cell survival. In the present study, we provide evidence that an E3C1 fragment suppresses Notch signaling and angiogenesis in explanted tumor model. Materials & Methods: Cells of the human oral squamous cell carcinoma cell line, SCCKN, were injected into nude mice to generate explanted tumors. cDNAs encoding, the E3 and C1 domains of Del1 (E3C1), were inserted into pcDNA3D (pE3C1) and injected into the tumors every 7 days with a transfection reagent, jet-PEI. Tumor angiogenesis was evaluated by immunohistochemistry with antibodies for PECAM, von Willebrand factor and PDGF-beta and intravenous injection of Lycopersicon esculentum lectin. The signal transduction of notch was analyzed by western blotting. Results: Treatment with pE3C1 suppressed the growth of explanted tumors and improved life prognosis of mice. In localization with immunostaining of PECAM or von Willebrand factor, and angioglaphy with Lycopersicon esculentum lectin, vasculature without lumen was increased by gene therapy of Del1 fragment. Among the treatment with pE3C1 and control, the PDGF beta staining cells, which is marker of tip cells in angiogenesis, were increased. Western blotting of human umbilical endothelial cells cultured with an E3C1 recombinant protein showed the decreased expression of active notch and hey1. Discussion: The phenotype of tumor vascular by treated with pE3C1 was analogous to the phenotype of inhibited of notch. In our study, it is suggested that the effective angiogenesis was inhibited by E3C1 inhibition of notch function. There is an anti-angiogenic domain, E3C1, adjacent to the RGD in E2 of Del1. The presence of domains with opposing activities next to one another in the same protein could account for the seemingly ambiguous characteristics of Del1 activity on angiogenesis. The EGF domain of Del1 has amino acid sequence, CXDXXXXYXCXC, which was shared by notch and delta. Signaling way of the motif should be investigated for notch function.
Azin Mirzadeh
General Dentist, USA
Title: Pregnancy tumor; a review of literature and a report of unusual case
Time : 17:20-17:35
Biography:
Azin Mirzadeh got her Doctoral degree in Dentistry from University of Medical Science and Health Services School of Dentistry, Kerman-Iran. She has 5 publications in fields of Oral Pathology, Periodontology and Endodontics. She was a member of scientific committee in Dental Disease Research Center in Kerman-Iran. She got honor and award as a patent in field of Oral Surgery, with the title of, “The arch bar applicator for oral and maxillofacial surgery”. She is a professional membership in Iranian General Dentist association (IGDA). In 2014, she moved to the United States, and now she in the application process for dental schools.
Abstract:
Pregnancy tumor histologically coincides with oral pyogenic granuloma. It is a reactive hemorrhagic swelling that mostly occurs in gingiva of pregnant women and can cause some complications. The tumor usually grows rapidly and direct relationship has been observed between the growth rate of the tumor and decreased level of estrogen and progesterone, occurring during the course of pregnancy. Gingiva is the most common site involved; it usually occurs labially on maxillary anterior teeth but the tongue, lips, palate and oral mucosa might also be rarely involved. This study aimed to describe an extra gingival pregnancy tumor occurred on the tongue in a 28 years old female patient at 7th month of gestation. The lesion mass was 1.5 cm in greatest diameter on the right side of the dorsum of the tongue with mild spontaneous bleeding and it interfered with speech and mastication. The lesion was excised under local anesthesia during the pregnancy with no untoward reactions. The histopathological examination revealed granulation tissue with non neoplastic proliferation of endothelial cells, suggestive of pregnancy tumor. During pregnancy, careful oral hygiene, removal of dental plaque and use of soft toothbrushes are very important to avoid occurrence of pregnancy tumor.
- Track 2: Hematopathology
Track 8: Anatomical Pathology
Track 6: Oral and Maxillofacial Pathology
Session Introduction
Hina Naushad Qureishi
University of Nebraska medical Center, USA
Title: Genomic signatures in non-hodgkin lymphomas
Time : 10:00-10:25
Biography:
Dr Hina Naushad Qureishi has completed her medical degree from Rawalpindi Medical College, Pakistan. She completed her pathology residency from University of Nebraska Medical Center in Omaha Nebraska, followed by a one-year surgical pathology fellowship at Washington University School of Medicine/Barnes-Jewish Hospital in St. Louis, MO. She also completed a two-year fellowship in hematopathology from University of Nebraska Medical Center. She worked as an assistant professor at Creighton University Medical Center in Omaha where she directed the flow cytometry and hematology laboratories and was also the director for M2 Hematology/Oncology course. Currently she is as an assistant professor in the division of hematopathology at University of Nebraska Medical Center.
Abstract:
The classification of B-cell and T-cell non-Hodgkin lymphoma has changed considerably over the last several decades. The currently used World Health Organization (WHO) classification system has a broader consensus among the clinical and biomedical community. However, there are still several challenges in regards to the understanding of tumor biology, clinical outcome and diagnostic accuracy in certain subtypes of lymphomas such as peripheral T-cell lymphoma (PTCL), where the diagnosis is frequently challenging even among expert hematopathologists and often time’s assessment requires additional molecular testing. Recently genome-wide high throughput techniques have greatly improved our understanding of B and T-cell lymphomas. This novel genetic information has not only aided in diagnosis, but has also revealed a landscape of critical molecular events that determine the biological and clinical behavior of a lymphoma. In this presentation, I will summarize the genetic characteristics of major subtypes of B-cell and T-cell lymphomas including diffuse large B cell lymphoma (DLBCL), follicular lymphoma (FL), Burkitt lymphoma (BL), and mantle cell lymphoma (MCL) and common subtypes of PTCL including angioimmunoblastic T-cell lymphoma (AITL), anaplastic T-cell lymphoma (ALCL), adult T-cell leukemia/lymphoma (ATLL) and extra-nodal NK/T cell lymphoma (ENKTL), and how can these improve precision in diagnosis and inform prognosis.
Leon P Bignold
University of Adelaide, Australia
Title: Mechanisms of action of carcinogens for the complexities of the tumor types
Time : 10:25-10:50
Biography:
Leon P Bignold graduated in Medicine from the University of Western Australia, and has post-graduate qualifications in internal medicine, experimental pathology, and diagnostic histopathology. From the 1980s, he has practiced and taught general and diagnostic histopathology at the University of Adelaide and the South Australian state government pathology service (SA Pathology, formerly Institute of Medical and Veterinary Science). He has written many articles on how genomic instability might explain the histopathological features of tumors, as well as related issues. In 2015, he published "Principles of Tumors: A Translational Approach to Foundations", Elsevier, Academic Press, Waltham, MA. With colleagues, he has also published a study of the origins of tumor pathology: "David Paul Hansemann: Contributions to Oncology" Birkhäuser, Basel, (2007) and a volume on the history of medicine: "Virchow's Eulogies" Birkhäuser, Basel, (2008). In 2006, he edited a volume “Cancer: cell structures, carcinogens and genomic instability”.
Abstract:
1. The etio-pathogenesis of tumors is thought to involve somatic mutations / genomic events, but how carcinogens induce genomic events is unclear. 2. For an agent to cause a tumor, five steps are involved (1): (i) The exogenous causative factor(s) enters, or perhaps only impinges on, a somatic cell. (ii) The exogenous agent(s) act on a critical structural or biochemical target(s) in the cell. (iii) A particular function of the target is disturbed. (iv) The disturbance in the function in the target has a pro-tumor genomic effect. (v) The relevant effect(s) / genomic event(s) produce the features of the thousand or so different types of tumors – from different parent cells, but nevertheless, all from the one genome. 3. This paper discusses the pathogenesis of chemical and radiation carcinogenesis under the following headings: (i) Toxicokinetics, including at the nuclear level (1). (ii) The intranuclear structures which may be affected. (iii) The action of carcinogens on susceptible nuclear component. (iiia) The dual dysfunction theory for uni-nucleotide events (1). (iiib) The tether drop theory for chromosomal aberration-like lesions (2). (iiic) The impaired polymerase complex theory for the focal replicative infidelity lesions (3).
Lorenzo Azzi
University of Insubria, Italy
Title: Starting from a cyst in the mandible
Time : 11:05-11:30
Biography:
Lorenzo Azzi is a PhD student of the “Biotechnology, Biosciences and Surgical Technology” course at University of Insubria. He is an oral surgeon and oral pathologist. He is assistant director of the Unit of Oral Pathology, Ospedale di Circolo Fondazione Macchi, Varese. He is active member of the Italian Society of Oral Pathology and Medicine (SIPMO) and of the European Association of Oral Medicine (EAOM)
Abstract:
We present a clinical case which deals with a 59-year-old female patient who presented at our Dental Clinic for a radiolucent bony lesion of the mandible with an odontogenic cyst-like appearance, accidentally detected by an orthopantomogram. First diagnosed as radicular cyst, after histological examination the lesion was identified as Central Giant Cell Granuloma (CGCG) of the mandible. Its aggressive recurrence and locally widespreading behaviour, followed by multi-focal involvement of the mandible, urged the oral pathologist to gather a multidisciplinary team of medical investigation and management, led by the dental practitioner himself in the early stages. Despite the fact that consultation with pathologists led to a full immunohistochemical characterization of the CGCG, the dentist suspected a more severe underlying condition than a CGCG of the jaw. Therefore he collected the x-rays of other body’s areas prescribed in the meantime by other specialists. A careful image comparison revealed the presence of multiple osteolytic lesions on the left knee. The cranial x-ray showed other bony lesions that gave the skull vault a “salt-and-pepper” appearance. Eventually, an haematochemical analysis confirmed the final diagnosis of the pathology, which could have quickly caused the patient’s death. The aim of this case presentation is to put on emphasize the enhancement of the role played by dental practitioners, especially oral surgeons and pathologists, during the diagnostic process in a multidisciplinary team of work. This presentation could be a clinicopathological debate involving discussion about the clinical case with a review of the corresponding pathology.
Priyanka Debta
Siksha ‘O’ Anusandhan University, India
Title: OSCC & myeloid cells (TATE & mast cells)
Biography:
Priyanka Debta has completed her MDS in Oral Pathology and Microbiology (2006-2009) from Deemed University S.P.D.C., India. She has done research in the field of forensic odontology & immunological cells infiltration in carcinoma and in odontogenic cysts. She has participated in national and international conferences and presented papers and posters. Presently she is working in I.D.S., SOA UNIVERSITY, BBSR, Odisha, India. Her various studies and reports have been published in the national/international reputed journals. She is a dedicated, resourceful and innovative instructor for her students that helps in intellectual growth by creating an atmosphere of mutual respect and open communication.
Abstract:
Background: Cancer is an important cause of morbidity and mortality. Oral squamous cell carcinoma is malignant neoplasm arising from mucosal epithelium of oral cavity. Despite enormous efforts to find a cure, overall survival of cancer patients has not increased and new therapeutic approaches are needed. The main barriers to successful product development are a limited understanding of the biology of tumors. So to understand the development of safe and effective cancer biotherapeutics, it is must to know each and every aspect of tumor cell biology. Bone marrow-derived myeloid cells such as macrophages, neutrophils, eosinophils, mast cells and dendritic cells infiltrate malignant tumors in large numbers and are sometimes a prominent feature in the stroma of such tissue. Aim: Evaluation of infiltration of myeloid cells (Tumor Associated Tissue Eosinophil & Mast cells) in different grades (WHO grading) of oral squamous cell carcinoma. Material & Methods: Histopathologically diagnosed 30 cases of OSCC were categorized in to: 10 cases of WDSCC, 10 cases of MDSCC and 10 cases of PDSCC. Hematoxylin and eosin stain was used to evaluate TATE & toluidine blue special stain was used to evaluate the mast cells infiltration. Follow up of cases were done for 3 years. Result: We found significant association of TATE & mast cells infiltration in OSCC cases. These myeloid cells infiltration significantly associated with age of patients but did not show any significant association with gender, site & habit of cases. When we compared these cells infiltration with clinical stages & different histological grades of tumor, we found their infiltration is decreasing; from stages 1 to stage 3 of tumor and from well to poorly differentiated carcinoma. We also found the less infiltration of these myeloid in recurrence cases of OSCC. Conclusion: We can easily evaluate the presence of TATE with routine H & E stain and toluidine blue is economic special stain to evaluate the mast cells. Thus routine assessment of these cells will be helpful to better understand their role in OSCC cases. In the future, assessment of these cells could become useful for therapeutic approach in this subset of patients.
- Young Researchers Forum
Session Introduction
Sanchari Saha
MGM Medical College, India
Title: Incidence of H. pylori in upper GI endoscopy biopsies: Prospective and retrospective study with emphasis on special staining methods
Time : 11:30-11:45
Biography:
Sanchari Saha has graduated from Kishanganj Medical College, India in 2013. She has then worked as a Houseman at Institute of Neurosciences, Kolkata for one year. Currently, she is pursuing MD in Pathology at MGM Medical College, India.
Abstract:
The present study includes retrospective and prospective study of 80 cases over a period of 5 years in Department of Pathology, MGM Medical College, Navi Mumbai. A total of 80 upper GI endoscopic biopsies were obtained from patients ranging between the age of 18-65 years with complaints of chronic upper abdominal symptoms, who were not suffering from active GI bleed, not on NSAIDS, not suffering from any systemic disease, who were non alcoholic or patients who underwent major Gastroduodenal surgery. The aim of study was to study the incidence of H. pylori in upper GI endoscopic biopsies. Identification of H. pylori with routine and special stains is to evaluate and correlate commonest symptoms of H. pylori infected patients and to study the age and sex distribution in H. pylori infection. We found 51 (63.8%) H. pylori positive cases and 29 (36.3%) H. pylori negative cases. This study was useful in diagnosing H. pylori in various gastric lesions. Routine H&E stain when supplemented with special stains like Warthin Starry, Modified Giemsa and Toluidine Blue helped in prompt identification of the pathogen, thereby alleviate the symptoms and prevent its sequelae. This study highlights the importance of incidence, endoscopic biopsies and identification of the bacilli, various gastric lesions and good comparison between different staining techniques such as H&E, Toluidine Blue, Modified Giemsa and Warthin Starry. It also includes the correlation of the endoscopic findings with histopathological interpretation of the endoscopic biopsies and also the analysis of the histopathological findings.
Kiranjeet Kaur
Post Graduate Institute of Medical Education and Research, India
Title: Unraveling the presence of sialoglycoconjugate specific antibodies in the serum samples of non-small cell lung cancer patients
Time : 11:45-12:00
Biography:
Kiranjeet Kaur has completed her Ph.D from Panjab University, India in 2014. She is currently working as pathology research assistant. She has published more than 10 papers in reputed journals and serving as an editorial board member of repute.
Abstract:
Aberrant glycosylation, in particular, alterations in sialylation status of glycans is a characteristic feature of cancer cells. Earlier studies in our laboratory have shown the presence of disease specific sialoglycoconjugate in Non-Small Cell Lung Cancer (NSCLC) cell lines. However, little progress has been made in the identification of disease specific antibodies (a potential alternative marker in diagnosis) against these glycoconjugates. Thus, in the present study an attempt was made to assess the status of the disease associated sialoglyconjugate specific antibodies in the serum samples of NSCLC patients (IgGp) and healthy individuals (IgGc). It was observed that the level of fetuin (broad spectrum sialoglycoconjugate) specific IgG was significantly higher than fetuin specific IgM and IgA in both the cases. The presence of fetuin/ganglioside specific IgG was higher in control samples as compared to NSCLC patients as assessed by ELISA. Further, the purification of IgGp and IgGc was carried out by subjecting the pooled sera to Protein A Sepharose CL-4B column, separately. Purified IgGc showed significantly high specificity to fetuin as well as ganglioside as compared to IgGp. The interaction of IgGp and IgGc was also checked with the cells/membrane proteins of NSCLC cell lines via ELISA, Western blotting & Immunocytochemistry. Both IgGp and IgGc interacted with the bands of ~91 kDa and ~76 kDa whereas IgGp also interacted with bands of ~66 kDa and ~45 kDa. The finding of the present study suggest that IgGp antibody may have the potential to serve as a unique probe for the detailed investigation of disease associated sialoglycoconjugates on NSCLC cells.
Sougata Ghosh
Savitribai Phule Pune University, India
Title: AucoreAgshell nanoparticles with potent antibiofilm activity as novel nanomedicine
Time : 12:00-12:15
Biography:
Sougata Ghosh has completed his BSc and MSc in Microbiology from Savitribai Phule Pune University, India. He is working on novel nanomaterial for disease control and bacterial pathogenesis in his PhD research. He has published 35 international research papers in peer reviewed international journals and filed 3 patents which are widely appreciated in various national and international conferences.
Abstract:
Medicinal plants serve as a rich source of diverse bioactive phytochemicals that might even take part in bioreduction and stabilization of phytogenic nanoparticles with immense therapeutic properties. Dioscorea bulbifera is a potent medicinal plant used in both Indian and Chinese traditional medicine owing to its rich phytochemical diversity. Herein, we report the rapid synthesis of novel AucoreAgshell DBTE). AucoreAgshell NPs synthesis was completed within 5 hours showing a prominent peak at 540 nm. The bioreduced nanoparticles were characterized using high resolution transmission electron microscopy (HRTEM), energy dispersive spectroscopy (EDS), dynamic light scattering (DLS), X-ray diffraction spectroscopy (XRD) and Fourier transform infrared spectroscopy (FTIR). The particles were further checked for antibiofilm activity against bacterial pathogens. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) was employed to study the mechanism behind antibiofilm activity. HRTEM analysis revealed 9 nm inner core of elemental gold covered by a silver shell giving a total particle diameter up to 15 nm. AucoreAgshell NPs were comprised of 57.34±1.01% gold and 42.66±0.97% silver of the total mass. AucoreAgshell NPs showed highest biofilm inhibition up to 83.68±0.09% against Acinetobacter baumannii. Biofilms of Pseudomonas aeruginosa, Escherichia coli and Staphylococcus aureus were inhibited up to 18.93±1.94%, 22.33±0.56% and 30.70±1.33%, respectively. Scanning electron microscopy (SEM) and atomic force microscopy (AFM) confirmed unregulated cellular efflux through pore formation leading to cell death. This is the first report of synthesis, characterization, antibiofilm and antileishmanial activity of AucoreAgshell NPs synthesized by D. bulbifera.