Downloaded from http://gut.bmj.com/ on June 14, 2016 - Published by group.bmj.com
Gut Online First, published on October 15, 2015 as 10.1136/gutjnl-2015-310456 GI cancer
ORIGINAL ARTICLE
Clinicopathological and molecular features of sessile serrated adenomas with dysplasia or carcinoma Mark Bettington,1,2,3 Neal Walker,1,2 Christophe Rosty,1,2 Ian Brown,2 Andrew Clouston,1,2 Diane McKeone,3 Sally-Ann Pearson,3 Barbara Leggett,1,3,4 Vicki Whitehall1,3,5 1
School of Medicine, The University of Queensland, Brisbane, Queensland, Australia 2 Envoi Specialist Pathologists, Brisbane, Queensland, Australia 3 The Conjoint Gastroenterology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia 4 The Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia 5 Department of Chemical Pathology, Pathology Queensland, Brisbane, Queensland, Australia Correspondence to Dr Mark Bettington, The Conjoint Gastroenterology Laboratory, Level 7, CBCRC, QIMR Berghofer Medical Research Institute, 300 Herston Road, Herston, Brisbane, QLD 4006, Australia;
[email protected],
[email protected] Received 28 July 2015 Revised 15 September 2015 Accepted 20 September 2015
ABSTRACT Objective Sessile serrated adenomas (SSAs) are the precursors of at least 15% of colorectal carcinomas, but their biology is incompletely understood. We performed a clinicopathological and molecular analysis of a large number of the rarely observed SSAs with dysplasia/ carcinoma to better define their features and the pathways by which they progress to carcinoma. Design A cross-sectional analysis of 137 SSAs containing regions of dysplasia/carcinoma prospectively collected at a community GI pathology practice was conducted. Samples were examined for BRAF and KRAS mutations, the CpG island methylator phenotype (CIMP) and immunostained for MLH1, p53, p16, β-catenin and 0-6-methylguanine DNA methyltransferase (MGMT). Results The median polyp size was 9 mm and 86.5% were proximal. Most were BRAF mutated (92.7%) and 94.0% showed CIMP. Mismatch repair deficiency, evidenced by loss of MLH1 (74.5%) is associated with older age (76.7 versus 71.0; p
