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More Frequent ß-Catenin Exon 3 Mutations in Gallbladder Adenomas Than in Carcinomas Indicate Different Lineages¹

Department of Pathology, Kitasato University School of Medicine, Kanagawa 228-8555, Japan

To clarify the contribution of ß-catenin, which is related to cell adhesion and intranuclear transcription, to gallbladder carcinogenesis, we investigated its expression using immunohistochemistry, and ß-catenin exon 3 mutations by DNA direct sequencing, in 18 gallbladder adenomas and 82 adenocarcinomas. Membranous expression was significantly lower in moderately and poorly differentiated than in well-differentiated adenocarcinoma cases (P < 0.001). The gallbladder adenomas showed significantly stronger expression 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 ß-catenin as a molecular marker, the adenoma-carcinoma sequence can be considered to be a minor pathway in gallbladder carcinogenesis.

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