Abstract
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.
Highlights
Mutation in exon 3 of b-catenin has been identified in approximately half of colorectal tumours that lack adenomatous polyposis coli (APC) mutations (Morin et al, 1997)
Nuclear localisation has been linked to progression of colorectal carcinogenesis when a certain threshold tumour size is exceeded (Brabletz et al, 2000)
Kobayashi et al (2000) have reported that nuclear translocation of b-catenin is involved in initiation of cancer in distinction to adenoma, independently of APC mutations
Summary
Mutation in exon 3 of b-catenin has been identified in approximately half of colorectal tumours that lack APC mutations (Morin et al, 1997). These b-catenin mutations involve alterations of exon 3 of serine/threonine sites that normally are phosphorylated by glycogen synthatase kinese 3b (GSK-3b). As phosphorylation of these sites is apparently necessary for APC-induced degradation of b-catenin (Morin et al, 1997), the b-catenin mutations cause intracellular b-catenin accumulation, increasing formation of the transcription-activating b-catenin/Tcf complex. The aim of this study was to examine intracellular localisation of b-catenin and to identify any mutations in exon 3 of b-catenin in SAs, by comparing the findings with those in CADs and carcinomas invading the submucosa (SCAs)
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