Hypermethylation of APC promoter 1A is associated with moderate activation of Wnt signalling pathway in a subset of colorectal serrated adenomas

Abstract

The role of Wnt signalling pathway in serrated adenomas (SAs) remains to be identified. The aim of this study was to determine whether Wnt signalling plays a role in the pathogenesis of SAs, and to clarify the mechanism of Wnt signalling activation in SAs. This study investigated immunoreactivities of adenomatous polyposis coli (APC) and beta-catenin, mutations of APC and beta-catenin genes, methylation status of APC promoter 1A in 12 SAs, and compared the findings with normal colorectal mucosa, hyperplastic polyps, traditional adenomas (TAs) and colorectal cancers (CRCs). APC expression was moderately decreased in SAs. Cytoplasmic accumulation of beta-catenin was demonstrated in 41.7% (5/12) of SAs, but membranous immunoreactivity of beta-catenin was lost in only 8.3% (1/12) of SAs. No beta-catenin mutation was detected in any of 12 SAs, and only one SA was found to be positive for APC gene mutation. Complete methylation of APC promoter 1A was found in 41.7% (5/12) of SAs, but in no TAs or CRCs. Hypermethylation of APC promoter 1A, instead of mutations involving APC and beta-catenin, contributes to moderate activation of Wnt signalling in a subset of SAs.