Altered expression of β-catenin without genetic mutation in intrahepatic cholangiocarcinoma

beta -catenin which has a role in E-cadherin mediated cell-to-cell adhesion, and is also involved in Wnt signaling pathways as a downstream signaling molecule accumulating in the cytoplasm and nucleus constitutively activates Tcf/LEF-associated transcription of oncogenic genes. We examined the expression pattern and the genetic alteration of beta -catenin to determine the role of beta -catenin in cancer formation and/or progression in intrahepatic cholangiocarcinoma (ICC). beta -catenin expression was immunohistochemically examined in 71 surgically resected ICC samples, and correlation between the expression pattern and clinicopathologic factors was investigated. Mutation analysis of beta -catenin exon 3, which included the responsible element for Wnt signaling was done in 55 samples, using PCRSSCP and direct sequence methods. Immunohistochemical analysis revealed the reduced membranous expression of beta -catenin in 58 (82%) ICCs and aberrant nuclear expression in 11 (15%) ICCs. The membranous expression was preserved in 62% of the papillary adenocarcinomas, and was frequently reduced in tumors with a poorer histological differentiation (84%), with a significant difference (P = .01). Genetic analysis showed that none of the 55 ICCs examined carried mutations in beta -catenin exon 3. The present study indicates that reduced membranous expression of beta -catenin is associated with non-papillary ICCs which have a more malignant behavior, and that nuclear translocation of beta -catenin results in oncogenic events. Mutations in beta -catenin exon 3 do not appear to be responsible for nuclear translocation of beta -catenin in ICCs.