More frequent beta-catenin exon 3 mutations in gallbladder adenomas than in carcinomas indicate different lineages

To clarify the contribution of beta -catenin, which is related to cell adhe sion and intranuclear transcription, to gallbladder carcinogenesis, we inve stigated its expression using immunohistochemistry, and beta -catenin exon 3 mutations by DNA direct sequencing, in 18 gallbladder adenomas and 82 ade nocarcinomas. Membranous expression was significantly lower in moderately a nd poorly differentiated than in well-differentiated adenocarcinoma cases ( P < 0.001). The gallbladder adenomas showed significantly stronger expressi on in the cytoplasm and the nucleus than carcinomas (P < 0.05 and P < 0.001 , respectively), and exon 3 mutations were observed in 62.5% (10 of 16) of adenomas, but only 4.8% (1 of 21) of carcinomas. With <beta>-catenin as a m olecular marker, the adenoma-carcinoma sequence can be considered to be a m inor pathway in gallbladder carcinogenesis.