No major tumorigenic role for β-catenin in serrated as opposed to conventional colorectal adenomas

Intracellular redistribution of β-catenin through mutation of the adenomatous polyposis coli (APC) gene has been proposed as an early tumorigenic event in most colorectal tumours. In serrated adenoma (SA), a newly recognised subtype of colorectal adenoma, APC mutations are uncommon, and the contribution of β-catenin to tumorigenesis remains unclear. We compared intracellular localisation of β-catenin and presence of mutations in exon 3 of β-catenin between 45 SAs, with 71 conventional adenomas (CADs), and eight carcinomas invading the submucosa (SCAs). Widespread or focal nuclear β-catenin expression was demonstrated in 7% of SAs (three out of 45), 61% of CADs (43 out of 71), and 88% of SCAs (seven out of eight). Cytoplasmic immunostaining for β-catenin was demonstrated in 16% of SAs (seven out of 45), 77% of CADs (55 out of 71), and 88% of SCAs (seven out of eight). No mutation in exon 3 of β-catenin was found in SAs or SCAs, while 7% of CADs (five out of 71) had β-catenin mutations. No nuclear or cytoplasmic expression of β-catenin was observed in the hyperplastic or conventionally adenomatous epithelium of mixed-type SAs. These findings suggest that β-catenin mutation is unlikely to contribute to the tumorigenesis in SA, and that intracellular localisation of β-catenin may not be associated with an early event of the tumour progression in most SAs.