Original Article
Mod Pathol 2001;14(9):900–905
Altered Expression of 
-Catenin without Genetic Mutation in Intrahepatic Cholangiocarcinoma
Keishi Sugimachi M.D.1, Ken-ichi Taguchi M.D.1, Shin-ichi Aishima M.D.1, Shinji Tanaka M.D., Ph.D.2, Mitsuo Shimada M.D., Ph.D.2, Kiyoshi Kajiyama M.D., Ph.D.2, Keizo Sugimachi M.D., Ph.D., FACS2 and Masazumi Tsuneyoshi M.D., Ph.D.1
- 1Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
- 2Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
Correspondence: Masazumi Tsuneyoshi M.D., Ph.D., Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. e-mail: masazumi@surgpath.med.kyushu-u.ac.jp; Fax: +81-92-642-5968
Accepted 10 May 2001.
Abstract
-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 -catenin to determine the role of -catenin in cancer formation and/or progression in intrahepatic cholangiocarcinoma (ICC). -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 -catenin exon 3, which included the responsible element for Wnt signaling was done in 55 samples, using PCR-SSCP and direct sequence methods. Immunohistochemical analysis revealed the reduced membranous expression of -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 -catenin exon 3. The present study indicates that reduced membranous expression of -catenin is associated with non-papillary ICCs which have a more malignant behavior, and that nuclear translocation of -catenin results in oncogenic events. Mutations in -catenin exon 3 do not appear to be responsible for nuclear translocation of -catenin in ICCs.
Keywords:
Intrahepatic cholangiocarcinoma (ICC), -catenin, Cell-to-cell adhesion, Nuclear translocation, Immunohistochemistry, PCR-SSCP, Direct sequence
