Frequent β-catenin aberration in human hepatocellular carcinoma

Recently, mutations in the beta -catenin gene in hepatocellular carcinoma (HCC) have been reported: approximately 20% of HCCs had activating mutations at the glycogen synthase kinase 3 beta phosphorylation sites within the exon 3 of the beta -catenin gene. However, changes in the level of the beta -catenin protein in HCC have not been well studied. We examined, by Western blotting, the expression level of the beta -catenin protein in cancerous tissues in comparison with that in adjacent non-cancerous tissues obtained from 32 cases of HCC with hepatitis C. An increase in the beta -catenin protein level in cancerous tissue compared to that in adjacent non-cancerous tissue was found in 15 (46.9%) of 32 cases of HCC. Mutation in exon 3 of the beta -catenin gene was found in six (18.8%) of the 32 cases, in five of which the beta -catenin protein level was increased. In total, beta -catenin aberration was found in 16 (50.0%) of 32 cases of HCC. It should be noted that beta -catenin aberration was also found in early HCC although it was observed chiefly in advanced HCCs. These results indicate that beta -catenin aberration is a frequent event in the development of HCC and may facilitate the development of HCC in the course of chronic hepatitis. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.