Immunohistochemical analysis and mutational analyses of beta-catenin, Axin family and APC genes in hepatocellular carcinomas

Yasuyo Ishizaki; Satoshi Ikeda; Masahiko Fujimori; Yosuke Shimizu; Takeshi Kurihara; Toshiyuki Itamoto; Akira Kikuchi; Masazumi Okajima; Toshimasa Asahara

Immunohistochemical analysis and mutational analyses of beta-catenin, Axin family and APC genes in hepatocellular carcinomas

Int J Oncol. 2004 May;24(5):1077-83.

Authors

Yasuyo Ishizaki¹, Satoshi Ikeda, Masahiko Fujimori, Yosuke Shimizu, Takeshi Kurihara, Toshiyuki Itamoto, Akira Kikuchi, Masazumi Okajima, Toshimasa Asahara

Affiliation

¹ Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.

PMID: 15067328

Abstract

Several lines of evidence show that the development of hepatocellular carcinoma (HCC) requires an accumulation of genetic alterations. However, molecular mechanism in HCC carcinogenesis remains unsolved. A total of 89 HCC samples were analyzed in this study to determine how alterations in the Wnt signaling pathway associate with the carcinogenesis of HCC. beta-catenin immunohistochemistry showed positive nuclear staining in 24 (27.0%) of the 89 HCC samples, indicating the existence of alterations in the Wnt signaling pathway in those 24 HCC samples. Mutations in the beta-catenin, Axin1 and Axin2 genes were detected in 10 (41.7%), 13 (54.2%) and 9 (37.5%) of the 24 beta-catenin-positive samples, respectively, but no mutation was detected in the APC gene. In conclusion, in addition to mutations in the beta-catenin gene, mutations in the Axin1 and Axin2 genes may alter the Wnt signaling pathway, resulting in accumulation of beta-catenin.

Publication types

Comparative Study
Research Support, Non-U.S. Gov't

MeSH terms

Adenomatous Polyposis Coli Protein / genetics
Adenomatous Polyposis Coli Protein / metabolism
Aged
Axin Protein
Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / metabolism
Carcinoma, Hepatocellular / pathology
Cytoskeletal Proteins / genetics*
Cytoskeletal Proteins / metabolism
DNA Mutational Analysis
DNA, Neoplasm / analysis
Female
Gene Expression Regulation, Neoplastic*
Humans
Immunoenzyme Techniques
Liver Neoplasms / genetics*
Liver Neoplasms / metabolism
Liver Neoplasms / pathology
Male
Middle Aged
Mutation / genetics*
Proto-Oncogene Proteins / metabolism
Repressor Proteins / genetics*
Repressor Proteins / metabolism
Signal Transduction
Trans-Activators / genetics*
Trans-Activators / metabolism
Wnt Proteins
beta Catenin

Substances

AXIN1 protein, human
AXIN2 protein, human
Adenomatous Polyposis Coli Protein
Axin Protein
CTNNB1 protein, human
Cytoskeletal Proteins
DNA, Neoplasm
Proto-Oncogene Proteins
Repressor Proteins
Trans-Activators
Wnt Proteins
beta Catenin