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 adhesion and intranuclear transcription, to gallbladder carcinogenesis, we investigated its expression using immunohistochemistry, and beta-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 beta-catenin as a molecular marker, the adenoma-carcinoma sequence can be considered to be a minor pathway in gallbladder carcinogenesis.
Yanagisawa
N
N
Department of Pathology, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan.
Mikami
T
T
Saegusa
M
M
Okayasu
I
I
D000236:Adenoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D019070:Cell Lineage / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics*; D005091:Exons; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D017422:Sequence Analysis, DNA; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin