Day 1 :
Keynote Forum
John E Tomaszewski
State University of New York at the University at Buffalo, USA
Keynote: Data fusion: A new paradigm for 21st century diagnostics
Time : 09:05-09:45
Biography:
John E Tomaszewski received his MD from the University of Pennsylvania, Philadelphia, PA in 1977. He is currently Professor and Chair of Pathology and Anatomical Sciences at the State University of New York at the University at Buffalo. He has published more than 300 papers in the domains of pathology diagnostics and the application of quantitative imaging to diagnostics.
Abstract:
Computational advances offer the promise of enabling the quantitative analysis of structural data at all levels of scale. In Pathology high-resolution cellular imaging methods including histology, super resolution optical, and electron microscopic examination can be married with other data using the new analytics of machine vision and machine learning. The computational analysis of structure offers incredible new tools with which to quantitatively mine the data within both macroscopic structure (101) and microscopic (10-6 to -9) worlds and integrate those data with other modes including molecular and cell biology information. In our work we seek to use quantitative histological image analysis for modeling complex biological systems. We do this starting with a fundamental hypothesis which is that a high-resolution image is a self-organizing set of data that uniquely represents all of the genes, all of the molecules, and all of the cells captured at one point in time. In other words, a histological image is what it is for very specific reasons and those reasons are the relationships amongst the genomics, epigenomics, proteomics, metabolomics, and all the “omics” that go into making that image. The promise of quantitative histological image analysis lies in the hypothesis that the linkages relating all of the molecular events contributing to an image are still extant and minable. This keynote address will review some of our work in this new domain of data fusion and integrated diagnostics.
Keynote Forum
Clay J Cockerell
Cockerell Dermatopathology, USA
Keynote: What’s new in diagnostic dermatology and dermatopathology
Time : 13:35-14:15
Biography:
Clay J Cockerell is a Clinical Professor of Dermatology and Pathology 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. He 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, he has overseen an educational program designed to train the next generation of dermatopathologists. He has served as an 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:
Objectives: become aware of new techniques available to assist in diagnosis and prognosis of melanomarnrnIn this lecture, a number of new cutaneous disorders recently described will be presented as well as information about new molecular techniques that have been recently developed that are now beginning to be introduced into dermatopathology and dermatology practicner.
- 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