Nuclear Beta-catenin Accumulation and Mutations of Beta-catenin and APC in Early Differentiated-type Tumors of the Stomach

Abstract

The beta-catenin and adenomatous polyposis coli (APC) genes are important in tumorigenesis of gastrointestinal neoplasms. Accumulation of beta-catenin in the nucleus due to mutations in beta-catenin and / or APC has been associated with early tumorigenesis in colorectal tumors. In this study, we investigated nuclear beta-catenin accumulation and mutations of beta-catenin and APC in 48 gastric adenomas and 59 early differentiated-type adenocarcinomas. Widespread or focal nuclear expression of beta-catenin was found in 14 (29.2%) gastric adenomas and 18 (30.5%) differentiated-type carcinomas. Mutations in beta-catenin were detected in only one case of gastric adenoma, while APC was mutated in 17 (35.4%) of the gastric adenomas and 11 (18.6%) early differentiated-type carcinomas. The accumulation of nuclear beta-catenin was significantly more prevalent in tumors with APC mutations than in those without APC mutations (67.9% vs 16.5%, p<0.0001) . These findings demonstrate that beta-catenin accumulation in the nucleus is an early and common event in the incipient phase of gastric differentiated-type tumorigenesis, and is associated not with mutations in the beta-catenin gene but with APC mutations.