Colorectal cancer Chapelle, J Clin Oncol, 2010
|
|
- Susanna Allen
- 6 years ago
- Views:
Transcription
1 Colorectal cancer Chapelle, J Clin Oncol, 2010
2 Early-Stage Colorectal cancer: Microsatellite instability, multigene assay & emerging molecular strategy Asit Paul, MD, PhD 11/24/15
3 Mr. X: A 50 yo asymptomatic male, MrX, underwent staging colonoscopy. Colonoscopy showed a 3 cm-mass in the sigmoid colon. Staging scans showed no adenopathy or distant metastases. CEA was 2.0 ng/ml (normal <3 ng/ml). Patient underwent sigmoid colonic resection. Pathology showed moderately differentiated adenocarcinoma, invading upto muscularis propria (pt2). 20 lymph nodes were retrieved and negative for metastasis. What is the next step to do? 1. Observation 2. Adjuvant chemotherapy 3. Testing for MMR protein 4. Testing for RAS and BRAF status
4 Mr. Y: A 45 yo M presented with 3 episodes of FBPR within a month. Colonoscopy with EUS showed a 4-cm ulcerating-mass obstructing the sigmoid colon, but no enlarged LN. Staging scans showed no adenopathy or distant metastases. CEA was 4.2 ng/ml (normal <3 ng/ml). Patient underwent R hemicolectomy with diverting colostomy. Pathology showed a mucinous adenocarcinoma with involvement of serosa (pt4). 27 lymph nodes were retrieved and negative for metastasis. What is the next step to do? 1. Observation 2. Adjuvant chemotherapy 3. Testing for MMR-protein 4. Multi-gene expression analysis
5 Current standard of care for non-metastatic CRC Stage I (T1/T2, Node negative): Surgery alone Stage II (T3/T4, Node-negative): Surgery ->?? Stage III (any N, Node positive) : Surgery + adjuvant chemotherapy
6 Adjuvant chemotherapy is stage II CRC could be beneficial, but the absolute benefit is small (5.4% highrisk, 3.6% low risk, over 5 years) Lancet, 2007, 370:
7 Adjuvant Chemotherapy Guidelines for stage II CRC High-risk stage II Colon cancer pt4 Tumor perforation Obstructing tumor Inadequate node sampling (<12 nodes)
8 Beyond the traditional measures of risk stratification.
9 Risk of recurrence in Stage II CRC patient in QUASAR study (n=1436) T4 status, MMR protein status & Recurrence score by multigene assay are the significant prognostic factors for recurrence Gray RG, J Clin Oncol, 2011
10 MMR & MSI Basics Testing strategy Clinical relevance
11 CRC carcinogenesis pathways Villar & Gruber, Nat Rev Oncol, 2010
12 Microsatellites Microsatellites are short (1-7 bp) repetitive nucleotide sequences scattered throughout human genome. There are estimated 500,000 microsatellites in human genome. Most common MS in human genome is a dinucloide-repeats of A & C Length of microsatellites varies from personto-person, but have a set length for an individual person ( DNA finger print ).
13 Microsatellite Instability (MSI) Microsatellites are prone to replication error Erroneous replication process leads to increase or decrease in number of repeats in MS known as microsatellite instability (MSI) Gruber, J Nat Cancer Inst, 2003
14 Consequence of MSI In most cases, MSI may not have any consequences. If MSI occurs in an important gene, it leads to disease. MSI was first described in XP. MSI in an oncogene or tumor suppressor gene increases the risk of cancer. Lynch syndrome is the classic example of MSI as a result of germline mutation of MMR gene
15 Mismatched Repair Proteins (MMR) MMR proteins are responsible for surveillance & correction of replicationerrors MMR proteins are products of 4 genes: MLH1, MSH2, MSH6, PMS2 Deficiency of MMR protein (MMR-d), due to mutation of MMR gene (germ line or sporadic), leads to replication error & MSI
16 Testing of MMR/MSI IHC of tumor tissue for MMR protein expressions MSI testing of tumor tissue A panel of microsatellite markers, is compared in tumor tissue and normal tissue. Core panel of five markers are generally used: BAT25, BAT26, D2S123, D5S346, and D17S250 DNA-based testing, PCR, gene-sequencing analysis (blood or tumor tissue) Chapelle, J Clin Oncol, 2010
17 MMR Proteins MMR proteins make heterodimers MLH1 & MSH2 are the dominant partner of their pair MSH6 & PMS2 proteins are unstable in absence of their dominant partners
18 IHC patterns of MMR protein expression Richman, Int J of Oncol, 2015
19 Mr. Z: A 51 yo M underwent staging colonoscopy. Colonoscopy showed a non-obstructing 3 cm-mass in the ascending colon. Staging scans showed no adenopathy or distant metastases. CEA was 3.0 ng/ml. Patient underwent colonic resection & anastomosis. Pathology showed mucinous adenocarcinoma, invading through muscularis propria to adjacent pericolonic tissue (pt3). 27 lymph nodes were retrieved and negative for metastasis. What is the next step to do? 1. Observation 2. Adjuvant chemotherapy 3. Testing for MMR proteins 4. Testing for RAS and BRAF status
20 Who should get testing for MMR/MSI Testing for MMR protein and/or MSI should be done for all patients with newlydiagnosed colorectal cancer ASCO, ESMO & ACG guidelines, 2014 Patients who are diagnosed with colorectal cancer <70 years, stage II tumors, or who meet the Bethesda Criteria NCCN, 2015
21 Phenotype of d-mmr/ MSI Infiltrating Mucinous differentiation Poorly differentiated with medullary growth pattern Crohn-like lymphocytic reaction Early age of onset, R sided tumors, synchronus or metachronus tumors, high-grade/low-stage
22 Mr. Z Mr. Z with pt3pn0m0 (stage II) colon cancer. His tumor resected tumor was tested for MMRprotein expression by IHC. Staining showed absence of MLH1 & PMS2-proteins, staining for MSH2 & MSH6 are positive. What to do next? 1. Observation 2. Adjuvant chemotherapy 3. MSI-testing of tumor tissue 4. Testing for BRAF mutation
23 IHC pattern in MMR deficiency MMR-intact: (MMR-i) All MMR proteins are present ->MSS MMR-deficient (MMR-d): 1 or more MMR protiens are deficient -> MSI
24 15% of CRCs are MMR-d (MSI) More commonly, MMR-d is sporadic & is due to hypermethylation of MLH1 gene promoter. Sporadic tumors often carry the BRAF V600E somatic mutation. Others have germ line mutation of MMR gene (MLH1,MSH2, MSH6, PMS2) i.e Lynch syndrome In case of MLH1-loss by IHC, BRAF testing should be done prior to testing for Lynch Syndrome
25 Majority of MMR deficiency are sporadic, not Lynch Syndrome Loss of MLH1: Check BRAF mutation first. If wt, genetic testing for LS Loss of MSH2, MSH6, PMS2: genetic testing for LS
26 Prognostic value of MMR/MSI status in CRC
27 N=607, 50 y or younger 17% patients have MSI MSI has independent survival advantage over other risk factors MSI tumors tend to metastasize to LNs less Gryffe, NEJM, 2000
28 Patients with stage II & III CRC & MSI-status have better prognosis n outcome HR CI Data type Dienstmann R, J Clin Oncol. 2015
29 MSI as a predictor of response to 5FU based chemotherapy Villar & Gruber, Nat Rev Oncol, 2010
30 Mr. Z Mr. Z with pt3pn0m0 (stage II) colon cancer. Patient s resected tumor was tested for MMR-protein expression by IHC. Staining showed absence of MLH1 & PMS2-proteins, staining for MSH2 & MSH6 are positive. BRAF mutation testing of the tumor was done, which came out to be mutated for BRAF 600E Based on the molecular markers, who has the best & worst prognosis 1. MMR-i (MSS), BRAF wt, R sided tumor 2. MMR-i (MSS), BRAF V600 E mutated, L sided tumor 3. MMR-d (MSI), BRAF wt, R sided tumor 4. MMR-d (MSI), BRAF V600E mutated, R sided tumor
31 Prognostic value of BRAF V600E mutation MSS- All site MSS- Left side MSS- Right side In stage II-III colorectal cancer, BRAF mutation was confirmed a marker of poor survival only in subpopulations involving microsatellite stable and left-sided tumors (n=1423, PET-ACC3 cohort). KRAS status had no prognostic value. Popovici, BMC cancer, 2013
32 BRAF V600E is considered poor prognostic factor in CRC Interpretation of BRAF V600E mutation should always be done in the context of MSI status in early CRC The prognostic effect of MSI in early CRC overrides poor prognosis determined by BRAF Worst prognosis is seen in patient with MMR-i (MSS) & L sided tumor Dienstmann R, J Clin Oncol. 2015
33 Mr. Q A 51 yo M underwent staging colonoscopy. Colonoscopy showed a non-obstructing 3 cm-mass in the sigmoid colon. Staging scans showed no adenopathy or distant metastases. CEA was 3.0 ng/ml. Patient underwent sigmoid colonic resection. Pathology showed mucinous adenocarcinoma, invading through muscularis propria to adjacent pericolonic tissue (pt3). 27 lymph nodes were retrieved and negative for metastasis. IHC showed expression of all 4 MMR proteins (MMR-i). 27 lymph nodes were retrieved and negative for metastasis. What is the next step to do? 1. Observation 2. Adjuvant chemotherapy 3. Molecular/genetic testing for MSI-status 4. Multi-gene assay
34 Multigene assay in CRC Dienstmann R, J Clin Oncol. 2015
35
36 Risk of recurrence in Stage II CRC patient who were treated with edrecolomab or observation in CALGB 9851 study (n=162) Recurrence score & 5 year risk of of recurrence Venook, J Clin Oncol. 2013
37 Incorporating RS & MMR-status in decision making of stage II CRC T4 tumor: High risk, independent of RS & MMR status Gene expression analysis in not needed Patient should receive adjuvant treatment T3 Tumor, MMR-deficient (MSI) Good outcome, adjuvant chemotherapy is not indicated T3 Tumor, MMR-intact (MSS) Standard risk patient Multigene assay can identify high risk patient
38 IHC of MMR proteins is recommended for all new patients with CRC MLH1 loss by IHC can be associated with germ-line mutation or sporadic mutation. Loss of MLH1 should have BRAF testing to rule out sporadic mutation Loss of MLH2, MSH2, PMS2 are due to germ line mutation. Germ line mutation of MMR-gene is the hall-mark of Lynch Syndrome. Patients with MMR-d/ MSI have better prognosis Patients with BRAF V600E mutation has poor prognosis, when combined with MSS state
39 Adjuvant chemotherapy in stage II CRC Dienstmann R, J Clin Oncol. 2015
40 Adjuvant chemotherapy Stage III (node-positive), CRC patients are at high risk & should receive adjuvant chemotherapy. In Stage II standard risk patients, MMR status & Multigene assay should be taken into consideration in deciding chemotherapy MMR-d (MSI) has good prognosis without adjuvant treatment in stage II CRC. Stage II, MMR-i(MSS) can be risk stratified using multigene assay To date, none of the multi-gene assay are predictive of treatment benefit & should always be used in conjunction with MMR status & clinico-pathologic variables
41 Emerging Molecular Strategy in CRC
42 Herzig & Vassiliki, J Surg Onc, 2015
43 Hereditary Colorectal Neoplasms The Genetics of Colorectal Cancer Jasperson K & Burt RW, Surg Oncol Clin N Am, 2015: 24: ACG clinical guideline Syngal et al, Am J Gastroenterol, 2015; 110: Genetic/familial high risk assessment, NCCN GeneReviews@ NCBI
44 Hereditary CRC 5-6% of all CRCs are associated with germ-line mutations, causing hereditary predisposition Lynch syndrome is the most common, accounting for 2-3% of all CRCs FAP patients account for <1% of CRCs Other hereditary CRCs are very rare
45 Jasperson, Sur Clin NA, 2015
46 Jasperson, Sur Clin NA, 2015
47 Life-time Risk of Cancers in Lynch Syndrome Kohlmann & Gruber, GeneReviews, 2011
48 6342 individuals from 147 families 31 families (21%) had at least 1 pancreas CA Kastrinos, JAMA, 2009
49 Indications of MSI testing to rule out Lynch Syndrome
50 Jasperson, Sur Clin NA, 2015
51 Questions?
High risk stage II colon cancer
High risk stage II colon cancer Joel Gingerich, MD, FRCPC Assistant Professor Medical Oncologist University of Manitoba CancerCare Manitoba Disclaimer No conflict of interests 16 October 2010 Overview
More informationCase Presentation Diana Lim, MBBS, FRCPA, FRCPath Senior Consultant Department of Pathology, National University Health System, Singapore Assistant Pr
Case Presentation Diana Lim, MBBS, FRCPA, FRCPath Senior Consultant Department of Pathology, National University Health System, Singapore Assistant Professor Yong Loo Lin School of Medicine, National University
More informationUniversal Screening for Lynch Syndrome
Universal Screening for Lynch Syndrome St. Vincent/Ameripath protocol proposal Lynch syndrome (HNPCC) 1/35 individuals with colorectal cancer has Lynch syndrome Over half individuals are >50 at time of
More informationA Review from the Genetic Counselor s Perspective
: A Review from the Genetic Counselor s Perspective Erin Sutcliffe, MS, CGC Certified Genetic Counselor Cancer Risk Evaluation Program INTRODUCTION Errors in base pair matching that occur during DNA replication,
More informationGuidelines for the assessment of mismatch repair (MMR) status in Colorectal Cancer
Guidelines for the assessment of mismatch repair (MMR) status in Colorectal Cancer Start date: May 2015 Review date: April 2018 1 Background Mismatch repair (MMR) deficiency is seen in approximately 15%
More informationSerrated Polyps and a Classification of Colorectal Cancer
Serrated Polyps and a Classification of Colorectal Cancer Ian Chandler June 2011 Structure Serrated polyps and cancer Molecular biology The Jass classification The familiar but oversimplified Vogelsteingram
More informationCOLORECTAL PATHWAY GROUP, MANCHESTER CANCER. Guidelines for the assessment of mismatch. Colorectal Cancer
COLORECTAL PATHWAY GROUP, MANCHESTER CANCER Guidelines for the assessment of mismatch repair (MMR) status in Colorectal Cancer January 2015 1 Background Mismatch repair (MMR) deficiency is seen in approximately
More informationCOLORECTAL PATHWAY GROUP, MANCHESTER CANCER. Guidelines for the assessment of mismatch. Colorectal Cancer
COLORECTAL PATHWAY GROUP, MANCHESTER CANCER Guidelines for the assessment of mismatch repair (MMR) status in Colorectal Cancer March 2017 1 Background Mismatch repair (MMR) deficiency is seen in approximately
More informationTumorNext-Lynch. genetic testing for hereditary colorectal or uterine cancer
TumorNet-Lynch genetic testing for hereditary colorectal or uterine cancer What Are the Causes of Hereditary Colorectal Cancer? sporadic 70% familial 20% hereditary 10% Lynch syndrome, up to 4% Familial
More informationDevelopment of Carcinoma Pathways
The Construction of Genetic Pathway to Colorectal Cancer Moriah Wright, MD Clinical Fellow in Colorectal Surgery Creighton University School of Medicine Management of Colon and Diseases February 23, 2019
More informationMicrosatellite instability and other molecular markers: how useful are they?
Microsatellite instability and other molecular markers: how useful are they? Pr Frédéric Bibeau, MD, PhD Head, Pathology department CHU de Caen, Normandy University, France ESMO preceptorship, Barcelona,
More informationAnatomic Molecular Pathology: An Emerging Field
Anatomic Molecular Pathology: An Emerging Field Antonia R. Sepulveda M.D., Ph.D. University of Pennsylvania asepu@mail.med.upenn.edu 2008 ASIP Annual Meeting Anatomic pathology (U.S.) is a medical specialty
More informationAssessment of Universal Mismatch repair (MMR) or Microsatellite Instability (MSI) testing in colorectal cancers.
Assessment of Universal Mismatch repair (MMR) or Microsatellite Instability (MSI) testing in colorectal cancers. Soheila Hamidpour MD, Madhusudhana S MD. MMR deficient colorectal tumors can be present
More informationGENETICS OF COLORECTAL CANCER: HEREDITARY ASPECTS By. Magnitude of the Problem. Magnitude of the Problem. Cardinal Features of Lynch Syndrome
GENETICS OF COLORECTAL CANCER: HEREDITARY ASPECTS By HENRY T. LYNCH, M.D. 1 Could this be hereditary Colon Cancer 4 Creighton University School of Medicine Omaha, Nebraska Magnitude of the Problem Annual
More informationGastric and Colon Cancer. Dr. Andres Wiernik 2017
Gastric and Colon Cancer Dr. Andres Wiernik 2017 GASTRIC CANCER Gastric Cancer Classification Epidemiology General principles of Management 25% GE Junction Gastric Cancer 75% Gastric Cancer Epidemiology
More informationWhat Pathology can tell us in the approach of localized colorectal cancer
What Pathology can tell us in the approach of localized colorectal cancer A/Prof Tony Lim Kiat Hon Department of Anatomical Pathology Singapore General Hospital ESMO 2017 Singapore Nov 1 2 Do we still
More informationMeasure Description. Denominator Statement
CMS ID/CMS QCDR ID: CAP 18 Title: Mismatch Repair (MMR) or Microsatellite Instability (MSI) Biomarker Testing to Inform Clinical Management and Treatment Decisions in Patients with Primary or Metastatic
More informationLynch Syndrome Screening for Endometrial Cancer: Basic Concepts 1/16/2017
1 Hi, my name is Sarah Kerr. I m a pathologist at Mayo Clinic, where I participate in our high volume Lynch syndrome tumor testing practice. Today I hope to cover some of the basics needed to understand
More informationColorectal Carcinoma Reporting in 2009
Colorectal Carcinoma Reporting in 2009 Overview Colorectal carcinoma- new and confusing AJCC TNM issues Wendy L. Frankel, M.D. Vice-Chair and Director of AP Department of Pathology The Ohio State University
More informationEarly colorectal cancer Quality and rules for a good pathology report Histoprognostic factors
Early colorectal cancer Quality and rules for a good pathology report Histoprognostic factors Frédéric Bibeau, MD, PhD Pathology department Biopathology unit Institut du Cancer de Montpellier France Quality
More informationResource impact report: Molecular testing strategies for Lynch syndrome in people with colorectal cancer (DG27)
Putting NICE guidance into practice Resource impact report: Molecular testing strategies for Lynch syndrome in people with colorectal cancer (DG27) Published: February 2017 Summary Molecular testing strategies
More informationImmunotherapy for dmmr metastatic colorectal cancer. Prof.dr. Kees Punt Dept. Medical Oncology AUMC
Immunotherapy for dmmr metastatic colorectal cancer Prof.dr. Kees Punt Dept. Medical Oncology AUMC Active specific immunotherapy (ASI) in stage II-III colon cancer Vaccination with autologous tumor + BCG
More informationINMUNOTERAPIA EN CANCER COLORRECTAL METASTASICO. CCRm MSI-H NUEVO ESTANDAR EN PRIMERA LINEA Y/O PRETRATADOS?
INMUNOTERAPIA EN CANCER COLORRECTAL METASTASICO CCRm MSI-H NUEVO ESTANDAR EN PRIMERA LINEA Y/O PRETRATADOS? V. Alonso Servicio de Oncologia Medica H. U. Miguel Servet Zaragoza MSI-H mcrc Clinical and Pathological
More informationImmunotherapy in Colorectal cancer
Immunotherapy in Colorectal cancer Ahmed Zakari, MD Associate Professor University of Central Florida, College of Medicine Medical Director, Gastro Intestinal Cancer Program Florida Hospital Cancer Institute
More informationMarcatori biomolecolari dei carcinomi del colon-retto sporadici ed ereditari
Marcatori biomolecolari dei carcinomi del colon-retto sporadici ed ereditari Milo Frattini XII Congresso AIFEG Villa Cagnola - Gazzada Schianno (VA) 16/17.10.2014 APC β-catenina APC Met (p16) Models of
More informationColorectal adenocarcinoma leading cancer in developed countries In US, annual deaths due to colorectal adenocarcinoma 57,000.
Colonic Neoplasia Remotti Colorectal adenocarcinoma leading cancer in developed countries In US, annual incidence of colorectal adenocarcinoma 150,000. In US, annual deaths due to colorectal adenocarcinoma
More informationIntroduction. Why Do MSI/MMR Analysis?
Clinical Significance Of MSI, KRAS, & EGFR Pathway In Colorectal Carcinoma UCSF & Stanford Current Issues In Anatomic Pathology Introduction Microsatellite instability and mismatch repair protein deficiency
More informationLOINC. Clinical information. RCPA code. Record if different to report header Operating surgeon name and contact details. Absent.
Complete as narrative or use the structured format below 55752-0 17.02.28593 Clinical information 22027-7 17.02.30001 Record if different to report header Operating surgeon name and contact details 52101004
More informationCurrent Status of Biomarkers (including DNA Tumor Markers and Immunohistochemistry in the Laboratory Diagnosis of Tumors)
Current Status of Biomarkers (including DNA Tumor Markers and Immunohistochemistry in the Laboratory Diagnosis of Tumors) Kael Mikesell, DO McKay-Dee Hospital May 14, 2015 Outline Update to DNA Testing
More informationColorectal Cancer Structured Pathology Reporting Proforma DD MM YYYY
Colorectal Cancer Structured Pathology Reporting Proforma Mandatory questions (i.e. protocol standards) are in bold (e.g. S1.03). Family name Given name(s) Date of birth DD MM YYYY S1.02 Clinical details
More informationColon Cancer Update Christie J. Hilton, DO
POMA Winter Conference Christie Hilton DO Medical Oncology January 2018 None Colon Cancer Numbers Screening (brief update) Practice changing updates in colon cancer MSI Testing Immunotherapy in Colon Cancer
More informationThird Line and Beyond: Management of Refractory Colorectal Cancer
Third Line and Beyond: Management of Refractory Colorectal Cancer George A. Fisher MD PhD Stanford University 1 Overview Defining the chemo refractory and intolerant Agents approved in 3 rd line setting
More informationRisk of Colorectal Cancer (CRC) Hereditary Syndromes in GI Cancer GENETIC MALPRACTICE
Identifying the Patient at Risk for an Inherited Syndrome Sapna Syngal, MD, MPH, FACG Director, Gastroenterology Director, Familial GI Program Dana-Farber/Brigham and Women s Cancer Center Associate Professor
More informationCorporate Medical Policy
Corporate Medical Policy Multigene Expression Assay for Predicting Recurrence in Colon File Name: Origination: Last CAP Review: Next CAP Review: Last Review: multigene_expression_assay_for_predicting_recurrence_in_colon_cancer
More informationThe Whys OAP Annual Meeting CCO Symposium September 20. Immunohistochemical Assessment Dr. Terence Colgan Mount Sinai Hospital, Toronto
Immunohistochemical Assessment of Mismatch Repair Proteins in Endometrial Cancer: The Whys and How Terence J. Colgan, MD Head of Gynaecological Pathology, Mount Sinai Hospital, University of Toronto, Toronto.
More informationLYNCH SYNDROME: IN YOUR FACE BUT LOST IN SPACE (MOUNTAIN)!
LYNCH SYNDROME: IN YOUR FACE BUT LOST IN SPACE (MOUNTAIN)! Kathryn Singh, MPH, MS, LCGC Associate Clinical Professor Assistant Director, Graduate Program in Genetic Counseling Division of Genetic and Genomic
More informationCaring for a Patient with Colorectal Cancer. Objectives. Poll question. UNC Cancer Network Presented on 10/15/18. For Educational Use Only 1
Caring for a Patient with Colorectal Cancer Tammy Triglianos RN, APRN-BC, AOCNP Nurse Practitioner, GI Oncology 10/15/2018 Objectives Describe common signs and symptoms of colorectal cancer Understand
More informationSignet-Ring Cell Carcinoma of the Colon: A Case Report and Review of the Literature
Published online: November 4, 2015 2015 The Author(s) Published by S. Karger AG, Basel 1662 6575/15/0083 0466$39.50/0 This article is licensed under the Creative Commons Attribution-NonCommercial 4.0 International
More informationAgenda 8:30 AM. Jennifer L. Hunt
Agenda Topic Introduction Terence J. Colgan Jennifer L. Hunt Time 8:30 AM Pre-analytic Variables in Molecular Testing Philip A. Branton 8:40 AM Carcinoma of Unknown Primary Site Is Gene Expression Profiling
More informationCOLORECTAL CANCER CASES
COLORECTAL CANCER CASES Case #1 Case #2 Colorectal Cancer Case 1 A 52 year-old female attends her family physician for her yearly complete physical examination. Her past medical history is significant
More informationNational Medical Policy
National Medical Policy Subject: Policy Number: Genetic Testing for Hereditary Nonpolyposis Colorectal Cancer (HNPCC) (Lynch Syndrome) NMP137 Effective Date*: April 2004 Updated: March 2017 This National
More informationMicrosatellite instability and other molecular markers: how usefulare they? Pr Frédéric Bibeau, MD, PhD Pathology Department CHU de Caen France
Microsatellite instability and other molecular markers: how usefulare they? Pr Frédéric Bibeau, MD, PhD Pathology Department CHU de Caen France Content - Colorectal cancer context - CRC molecular classification
More informationContent. Diagnostic approach and clinical management of Lynch Syndrome: guidelines. Terminology. Identification of Lynch Syndrome
of Lynch Syndrome: guidelines 17/03/2009 Content Terminology Lynch Syndrome Presumed Lynch Syndrome Familial Colorectal Cancer Identification of Lynch Syndrome Amsterdam II criteria Revised Bethesda Guidelines
More informationColorectal Cancer - Working in Partnership. David Baty Genetics, Ninewells Hospital
Colorectal Cancer - Working in Partnership David Baty Genetics, Ninewells Hospital Genetics and Pathology National initiatives Colorectal cancer Inherited CRC Sporadic CRC The Liquid Biopsy The future?
More informationGuidelines on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer
s on Genetic Evaluation and Management of Lynch Syndrome: A Consensus Statement by the US Multi-Society Task Force on Colorectal Cancer Francis M. Giardiello, MD, 1 John I. Allen, 2 Jennifer E. Axilbund,
More informationFamilial and Hereditary Colon Cancer
Familial and Hereditary Colon Cancer Aasma Shaukat, MD, MPH, FACG, FASGE, FACP GI Section Chief, Minneapolis VAMC Associate Professor, Division of Gastroenterology, Department of Medicine, University of
More informationDisclosures. Clinical and molecular features to guide adjuvant therapy. Personalized Medicine - Decision Tools -
Disclosures Clinical and molecular features to guide adjuvant therapy Daniel Sargent Professor of Biostatistics & Oncology Mayo Clinic Consulting activities Amgen Pfizer Roche/Genentech Sanofi-Aventis
More informationAdjuvant/neoadjuvant systemic treatment of colorectal cancer
5th ESO-ESMO Eastern Europe and Balkan Region Masterclass in Medical Oncology Belgrade, June 19 th 2018 Adjuvant/neoadjuvant systemic treatment of colorectal cancer Carlotta Antoniotti Polo Oncologico
More informationCase Study. Overview. Deleterious MLH1 mutation detected on sequencing 10/16/2014
The Role of Next Generation Sequencing for Hereditary Cancer Syndromes: A Focus on Endometrial Cancer Laura J. Tafe, MD Assistant Professor of Pathology Assistant Director, Molecular Pathology Dartmouth-Hitchcock
More informationHisto-prognostic factors what histopathology has to offer for clinical decision making
Histo-prognostic factors what histopathology has to offer for clinical decision making Daniela E. Aust Institute for Pathology, University Hospital Dresden, Germany Center for Molecular Tumor Diagnostics
More informationFamilial and Hereditary Colon Cancer
Familial and Hereditary Colon Cancer Aasma Shaukat, MD, MPH, FACG, FASGE, FACP GI Section Chief, Minneapolis VAMC Associate Professor, Division of Gastroenterology, Department of Medicine, University of
More informationBy: Tania Cortas, MD Arizona Oncology 03/10/2015
By: Tania Cortas, MD Arizona Oncology 03/10/2015 Epidemiology In the United States, CRC incidence rates have declined about 2 to 3 percent per year over the last 15 years Death rates from CRC have declined
More informationHereditary Non Polyposis Colorectal Cancer(HNPCC) From clinic to genetics
From clinic to genetics Question 1) Clinical pattern of inheritance of the HNPCC-Syndrome? Question 1) Clinical pattern of inheritance of the HNPCC-Syndrome? Autosomal dominant Question 2) Incidence of
More informationA916: rectum: adenocarcinoma
General facts of colorectal cancer The colon has cecum, ascending, transverse, descending and sigmoid colon sections. Cancer can start in any of the r sections or in the rectum. The wall of each of these
More informationProgress towards an individualized approach to therapy: colorectal cancer
Progress towards an individualized approach to therapy: colorectal cancer Alan P. Venook, M.D. University of California, SF GIST: PET change after 4 weeks imatinib Multiple liver and upper abdominal 18
More informationWHAT SHOULD WE DO WITH TUMOUR BUDDING IN EARLY COLORECTAL CANCER?
CANCER STAGING TNM and prognosis in CRC WHAT SHOULD WE DO WITH TUMOUR BUDDING IN EARLY COLORECTAL CANCER? Alessandro Lugli, MD Institute of Pathology University of Bern Switzerland Maastricht, June 19
More informationcase report Reprinted from August 2013
Reprinted from August 2013 A 48-year-old woman with endometrial cancer Importance of screening for Lynch syndrome in patients with EC CAP TODAY and the Association for Molecular Pathology have teamed up
More informationPrecision Genetic Testing in Cancer Treatment and Prognosis
Precision Genetic Testing in Cancer Treatment and Prognosis Deborah Cragun, PhD, MS, CGC Genetic Counseling Graduate Program Director University of South Florida Case #1 Diana is a 47 year old cancer patient
More informationMolecular biology of colorectal cancer
Molecular biology of colorectal cancer Phil Quirke Yorkshire Cancer Research Centenary Professor of Pathology University of Leeds, UK Rapid pace of molecular change Sequencing changes 2012 1,000 genomes
More informationMSI and other molecular markers: how useful are they? Daniela E. Aust, Institute for Pathology, University Hospital Dresden, Germany
MSI and other molecular markers: how useful are they? Daniela E. Aust, Institute for Pathology, University Hospital Dresden, Germany Disclosure slide I Member of advisory boards for AMGEN, ROCHE I Speaker
More informationMolecular markers in colorectal cancer. Wolfram Jochum
Molecular markers in colorectal cancer Wolfram Jochum Biomarkers in cancer Patient characteristics Tumor tissue Normal cells Serum Body fluids Predisposition Diagnostic marker Specific diagnosis Prognostic
More informationMolecular subtyping: how useful is it?
Molecular subtyping: how useful is it? Daniela E. Aust, Institute for Pathology, University Hospital Dresden, Germany Center for Molecular Tumor Diagnostics at the NCT-Partner Site Dresden CMTD Disclosure
More informationGenetic testing all you need to know
Genetic testing all you need to know Sue Clark Consultant Colorectal Surgeon, St Mark s Hospital, London, UK. Colorectal cancer Familial 33% Polyposis syndromes
More informationMultiple localized metachronous recurrences in a patient of colon cancer and therapeutic controversies in stage II colon cancer
Case Report Multiple localized metachronous recurrences in a patient of colon cancer and therapeutic controversies in stage II colon cancer Vijai Simha, Rakesh Kapoor, Saniya Sharma Post Graduate Institute
More informationWhere are we in 2013?
The Use of Gene Profile Testing in the Adjuvant Therapy of Stages II & III Colon Cancer: Where are we in 2013? Howard S. Hochster, MD Professor of Medicine, Yale School of Medicine Associate Director,
More informationDavid P. Ryan, M.D. Clinical Director, MGH Cancer Center Chief, Hematology-Oncology, MGH
Colon Cancer 2015 David P. Ryan, M.D. Clinical Director, MGH Cancer Center Chief, Hematology-Oncology, MGH Colon Cancer Case presentation 72yo woman presented 1/03 abd discomfort and nausea Found to have
More informationMolecular Diagnosis for Colorectal Cancer Patients
Molecular Diagnosis for Colorectal Cancer Patients Antonia R. Sepulveda MD, PhD, FCAP October, 20, 2010 www.cap.org Welcome to the PHC Webinar Series This talk on The Molecular Diagnosis for Colorectal
More informationJoseph Misdraji, M.D. GI pathology Unit Massachusetts General Hospital
Joseph Misdraji, M.D. GI pathology Unit Massachusetts General Hospital jmisdraji@partners.org Low-grade appendiceal mucinous neoplasm (LAMN) High-grade appendiceal mucinous neoplasm (HAMN) Adenocarcinoma
More informationMultigene Expression Assay for Predicting Recurrence in Colon Cancer
MP 2.04.49 Multigene Expression Assay for Predicting Recurrence in Colon Cancer Medical Policy Section Medicine Issue 12:201312:2013 Subsection Original Policy Date 12:2013 Last Review Status/Date Reviewed
More informationPolicy Specific Section: Medical Necessity and Investigational / Experimental. October 14, 1998 March 28, 2014
Medical Policy Genetic Testing for Colorectal Cancer Type: Medical Necessity and Investigational / Experimental Policy Specific Section: Laboratory/Pathology Original Policy Date: Effective Date: October
More informationcolorectal cancer Colorectal cancer hereditary sporadic Familial 1/12/2018
colorectal cancer Adenocarcinoma of the colon and rectum is the third most common site of new cancer cases and deaths in men (following prostate and lung or bronchus cancer) and women (following breast
More informationHow common are mutations in the MSH2 gene? 1. Mutations that cause Lynch syndrome are rare found in approximately 1 in 370 individuals.
The gene is a tumor suppressor gene. Tumor suppressor genes slow down cell division, repair DNA mistakes, or tell cells when to die. When they don't work properly, cells can grow out of control, which
More informationB Base excision repair, in MUTYH-associated polyposis and colorectal cancer, BRAF testing, for hereditary colorectal cancer, 696
Index Note: Page numbers of article titles are in boldface type. A Adenomatous polyposis, familial. See Familial adenomatous polyposis. Anal anastomosis, ileal-pouch, proctocolectomy with, in FAP, 591
More informationComparison of the Mismatch Repair System between Primary and Metastatic Colorectal Cancers Using Immunohistochemistry
Journal of Pathology and Translational Medicine 2017; 51: 129-136 ORIGINAL ARTICLE Comparison of the Mismatch Repair System between Primary and Metastatic Colorectal Cancers Using Immunohistochemistry
More informationGeneral Surgery Grand Grounds
General Surgery Grand Grounds University of Colorado Health Sciences Center Case Presentation December 24, 2009 Adam Lackey, PGY-5 J.L. - 2111609 27 YO female with chief complaint of abdominal pain. PMHx:
More informationColon cancer: practical molecular diagnostics. Wade S. Samowitz, M.D. University of Utah and ARUP
Colon cancer: practical molecular diagnostics Wade S. Samowitz, M.D. University of Utah and ARUP Disclosure Dr. Samowitz may receive royalties in the future related to the Ventana BRAF V600E antibody.
More informationMismatch Repair Deficiency Testing for Patients with Colorectal Cancer: A Clinical and Cost-Effectiveness Evaluation
CADTH Optimal Use Report Mismatch Repair Deficiency Testing for Patients with Colorectal Cancer: A Clinical and Cost-Effectiveness Evaluation September 2015 Volume 5, Issue 3a PROSPERO Registration Number:
More informationClinicopathologic Characteristics of Left-Sided Colon Cancers with High Microsatellite Instability
The Korean Journal of Pathology 29; 43: 428-34 DOI: 1.4132/KoreanJPathol.29.43.5.428 Clinicopathologic Characteristics of Left-Sided Colon Cancers with High Microsatellite Instability Sang Kyum Kim Junjeong
More informationBiomarkers to optimize treatment selection in colorectal cancer Edwin Pun HUI, MBChB, MD, FRCP (Lond & Edin)
Recent advances in the management of CRC II 2017/12/17 (Sun.) 10:10-11:00 Biomarkers to optimize treatment selection in colorectal cancer Edwin Pun HUI, MBChB, MD, FRCP (Lond & Edin) Department of Clinical
More informationCOLON CANCER GENETICS (FOR SURGEONS) Mark W. Arnold MD Chief, Division of Colon and Rectal Surgery Professor of Surgery The Ohio State University
COLON CANCER GENETICS (FOR SURGEONS) Mark W. Arnold MD Chief, Division of Colon and Rectal Surgery Professor of Surgery The Ohio State University 1. I am a surgeon; of course I have nothing to disclose.
More informationThe pathological phenotype of colon cancer with microsatellite instability
Dan Med J 63/2 February 2016 danish medical JOURNAL 1 The pathological phenotype of colon cancer with microsatellite instability Helene Schou Andersen 1, 2, Claus Anders Bertelsen 1, Rikke Henriksen 1,
More informationCASE STUDIES IN COLORECTAL CANCER: A ROUNDTABLE DISCUSSION
CASE STUDIES IN COLORECTAL CANCER: A ROUNDTABLE DISCUSSION PROVIDED AS AN EDUCATIONAL SERVICE BY THE INSTITUTE FOR CONTINUING HEALTHCARE EDUCATION SUPPORTED BY AN EDUCATIONAL GRANT FROM GENENTECH LEARNING
More informationManagement of higher risk of colorectal cancer. Huw Thomas
Management of higher risk of colorectal cancer Huw Thomas Colorectal Cancer 41,000 new cases pa in UK 16,000 deaths pa 60% 5 year survival Adenoma-carcinoma sequence (Morson) Survival vs stage (Dukes)
More informationCOLON CANCER & GENETICS VERMONT COLORECTAL CANCER SUMMIT NOVEMBER 15, 2014
COLON CANCER & GENETICS VERMONT COLORECTAL CANCER SUMMIT NOVEMBER 15, 2014 WENDY MCKINNON, MS, CGC CERTIFIED GENETIC COUNSELOR FAMILIAL CANCER PROGRAM UNIVERSIT Y OF VERMONT MEDICAL CENTER 1 CHARACTERISTICS
More informationMolecular Biomarkers in the Characterization & Treatment of Colorectal Carcinoma
Molecular Biomarkers in the Characterization & Treatment of Colorectal Carcinoma Andrew C. Nelson, M.D., Ph.D. Divisions of Anatomic & Molecular Pathology Department of Laboratory Medicine & Pathology
More informationMr Chris Wakeman. General Surgeon University of Otago, Christchurch. 12:15-12:40 Management of Colorectal Cancer
Mr Chris Wakeman General Surgeon University of Otago, Christchurch 12:15-12:40 Management of Colorectal Cancer Bowel cancer Chris Wakeman Colorectal Surgeon Christchurch Sam Simon (Simpsons) Elizabeth
More informationOncotype DX : Scientific Publications and Presentations
Oncotype DX : Scientific Publications and Presentations www.oncotypedx.com Oncotype DX : Scientific Publications and Presentations A Tool for Individualized Colon Cancer Treatment The Oncotype DX Colon
More informationDiagnostics guidance Published: 22 February 2017 nice.org.uk/guidance/dg27
Molecular testing strategies for Lynch syndrome in people with colorectal cancer Diagnostics guidance Published: 22 February 2017 nice.org.uk/guidance/dg27 NICE 2018. All rights reserved. Subject to Notice
More informationDIAGNOSTICS ASSESSMENT PROGRAMME Diagnostics consultation document
NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE DIAGNOSTICS ASSESSMENT PROGRAMME Diagnostics consultation document Molecular testing strategies for Lynch syndrome in The National Institute for Health
More informationEarly (and not so early) colorectal cancer: The pathologist s point of view
Early (and not so early) colorectal cancer: The pathologist s point of view Daniela E. Aust, Institute for Pathology, University Hospital Dresden, Germany Disclosure slide I Member of advisory board for
More informationGeneral Session 7: Controversies in Screening and Surveillance in Colorectal Cancer
General Session 7: Controversies in Screening and Surveillance in Colorectal Cancer Complexities of Pathological Assessment: Serrated Polyps/Adenomas Carolyn Compton, MD, PhD Professor of Life Sciences,
More informationMismatch repair status, inflammation and outcome in patients with primary operable colorectal cancer
Mismatch repair status, inflammation and outcome in patients with primary operable colorectal cancer Park JH, Powell AG, Roxburgh CSD, Richards CH, Horgan PG, McMillan DC, Edwards J James Park Clinical
More informationAllinaHealthSystems 1
Overview Biology and Introduction to the Genetics of Cancer Denise Jones, MS, CGC Certified Genetic Counselor Virginia Piper Cancer Service Line I. Our understanding of cancer the historical perspective
More informationGenetic Testing for Lynch Syndrome And Other Inherited Colon Cancer Syndromes
Genetic Testing for Lynch Syndrome And Other Inherited Colon Cancer Syndromes Policy Number: Original Effective Date: MM.02.007 09/01/2011 Line(s) of Business: Current Effective Date: HMO; PPO; QUEST Integration
More informationGenetic Testing for Lynch Syndrome and Other Inherited Colon Cancer Syndromes
Genetic Testing for Lynch Syndrome and Other Inherited Colon Cancer Syndromes Policy Number: 2.04.08 Last Review: 1/2018 Origination: 1/2004 Next Review: 1/2019 Policy Blue Cross and Blue Shield of Kansas
More informationLynch Syndrome. Angie Strang, PGY2
Lynch Syndrome Angie Strang, PGY2 Background Previously hereditary nonpolyposis colorectal cancer Autosomal dominant inherited cancer susceptibility syndrome Caused by defects in the mismatch repair system
More informationColon Cancer and Hereditary Cancer Syndromes
Colon Cancer and Hereditary Cancer Syndromes Gisela Keller Institute of Pathology Technische Universität München gisela.keller@lrz.tum.de Colon Cancer and Hereditary Cancer Syndromes epidemiology models
More informationKolorektalni karcinom- novosti u liječenju. PANEL: Maja Banjin, Janja Ocvirk, Borislav Belev, Ivan Nikolić, Anes Pašić
Kolorektalni karcinom- novosti u liječenju PANEL: Maja Banjin, Janja Ocvirk, Borislav Belev, Ivan Nikolić, Anes Pašić Kolorektalni karcinomnovosti u liječenju PANEL : Maja Banjin, Janja Ocvirk, Borislav
More informationDisclosure slide I Member of advisory board for AMGEN, ROCHE, BOEHRINGER I Speaker honoraria from FALK Pharma, Pfizer, Lilly and ROCHE I Third party f
Early (and not so early) colorectal cancer: The pathologist s point of view Daniela E. Aust, Institute for Pathology, University Hospital Dresden, Germany Disclosure slide I Member of advisory board for
More informationMismatch Repair Deficiency Tumour Testing for Patients with Colorectal Cancer: Recommendations
CADTH Optimal Use Report Mismatch Repair Deficiency Tumour Testing for Patients with Colorectal Cancer: Recommendations Draft Recommendations Report April 2016 Cite as: Canadian Agency for Drugs and Technologies
More information