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Serrated polyps of the large intestine: a molecular study comparing sessile serrated adenomas and hyperplastic polyps
Author(s) -
Sandmeier Dominique,
Benhattar Jean,
Martin Patricia,
Bouzourene Hanifa
Publication year - 2009
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2009.03356.x
Subject(s) - mlh1 , microsatellite instability , kras , hyperplastic polyp , methylation , cancer research , msh2 , cdkn2a , dna methylation , biology , pathology , mutation , gene , dna mismatch repair , colorectal cancer , medicine , cancer , gene expression , genetics , microsatellite , colonoscopy , allele
Aims: To compare the molecular profile of a series of sessile serrated adenomas (SSAs) and hyperplastic polyps (HPs), in order to distinguish these lesions, SSAs having a potential role in the genesis of serrated adenocarcinomas through a serrated pathway in which methylation plays a key role. Methods and results: Twelve HPs and sixteen SSAs of the right and left colon were investigated for microsatellite instability, DNA mismatch repair genes, p53, p16, and β‐catenin expression, MLH1 and p16 ( CDKN2A ) gene methylation, and KRAS and BRAF mutations. Both SSAs and HPs were microsatellite stable. MLH1 and MSH2 protein silencing , aberrant cytoplasmic expression and methylation of p16 were found to be exclusive to right‐sided SSAs. The MLH1 promoter gene was frequently methylated in right‐sided SSAs in contrast with HPs. Abnormal p53 and β‐catenin expression was present in both SSAs and HPs. BRAF and KRAS mutation were mutually exclusive, but KRAS mutation was present only in left‐sided SSAs and HPs. Conclusions: HPs and SSAs may be related lesions. However, at least right‐sided SSAs differ from left‐sided SSAs and HPs in the occurrence of MLH1 and p16 methylation, supporting the hypothesis that SSAs could be precursors of serrated adenocarcinomas.