Altered expression of beta-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 expre ssion pattern and the genetic alteration of beta -catenin to determine the role of beta -catenin in cancer formation and/or progression in intrahepati c cholangiocarcinoma (ICC). beta -catenin expression was immunohistochemica lly examined in 71 surgically resected ICC samples, and correlation between the expression pattern and clinicopathologic factors was investigated. Mut ation analysis of beta -catenin exon 3, which included the responsible elem ent for Wnt signaling was done in 55 samples, using PCRSSCP and direct sequ ence methods. Immunohistochemical analysis revealed the reduced membranous expression of beta -catenin in 58 (82%) ICCs and aberrant nuclear expressio n in 11 (15%) ICCs. The membranous expression was preserved in 62% of the p apillary adenocarcinomas, and was frequently reduced in tumors with a poore r histological differentiation (84%), with a significant difference (P = .0 1). Genetic analysis showed that none of the 55 ICCs examined carried mutat ions in beta -catenin exon 3. The present study indicates that reduced memb ranous expression of beta -catenin is associated with non-papillary ICCs wh ich 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.