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Gut. 2017 Jan;66(1):97-106. doi: 10.1136/gutjnl-2015-310456. Epub 2015 Oct 15.

Clinicopathological and molecular features of sessile serrated adenomas with dysplasia or carcinoma.

Author information

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.

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<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.

KEYWORDS:

COLON CARCINOGENESIS; COLONIC NEOPLASMS; COLONIC POLYPS; COLORECTAL CANCER GENES

PMID:
26475632
DOI:
10.1136/gutjnl-2015-310456
[Indexed for MEDLINE]

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