PT  - JOURNAL ARTICLE
AU  - Bettington, Mark
AU  - Walker, Neal
AU  - Rosty, Christophe
AU  - Brown, Ian
AU  - Clouston, Andrew
AU  - McKeone, Diane
AU  - Pearson, Sally-Ann
AU  - Leggett, Barbara
AU  - Whitehall, Vicki
TI  - Clinicopathological and molecular features of sessile serrated adenomas with dysplasia or carcinoma
AID  - 10.1136/gutjnl-2015-310456
DP  - 2017 Jan 01
TA  - Gut
PG  - 97--106
VI  - 66
IP  - 1
4099  - http://gut.bmj.com/content/66/1/97.short
4100  - http://gut.bmj.com/content/66/1/97.full
SO  - Gut2017 Jan 01; 66
AB  - 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<0.0029), female gender (70% versus 36%; p<0.0008), proximal location (91% versus 72%; p<0.02), CIMP (98% versus 80%; p<0.02) and lack of aberrant p53 (7% versus 34%; p<0.001) when compared with the mismatch repair-proficient cases. Loss of p16 (43.1%) and gain of nuclear β-catenin (55.5%) were common in areas of dysplasia/cancer, irrespective of mismatch repair status.Conclusions SSAs containing dysplasia/carcinoma are predominantly small (<10 mm) and proximal. The mismatch repair status separates these lesions into distinct clinicopathological subgroups, although WNT activation and p16 silencing are common to both. Cases with dysplasia occur at a similar age to cases with carcinoma. This, together with the rarity of these ‘caught in the act’ lesions, suggests a rapid transition to malignancy following a long dwell time as an SSA without dysplasia.