Mutation and overexpression of the β-catenin gene may play an important role in primary hepatocellular carcinoma among Chinese people

Abstract

Aim: To study the role of β-catenin gene mutation and expression in hepatocellular carcinogenesis. Method: Thirty-four hepatocellular carcinoma (HCC) specimens and adjacent para-cancerous tissues, and four normal liver tissues were analyzed. Subcellular distribution of β-catenin was examined by immunohistochemistry staining. Mutation and semiquantitative expression of β-catenin gene exon 3 mRNA were detected by RT-PCR-SSCP and in situ hybridization. Result: Immunohistochemistry showed that all normal liver tissues and para-cancerous tissues examined showed membranous-type staining for β-catenin protein, frequently with weak expression in the cytoplasm, but no β-catenin accumulation in nuclei was found; while in liver cancer, 21 cases (61.8%) of HCC examined showed accumulated type in cytoplasms or nuclei. On SSCP, 15 cases (44.1%) of HCC altogether displayed three kinds of characteristic mutational mobility shifts. No abnormal shifting bands were found in tissues from normal liver or para-cancerous area. The β-catenin gene exon 3 mRNA expression index of 34 HCCs was higher than that of para-cancerous tissue and normal liver tissue. Using in situ hybridization, the signal corresponding to β-catenin gene exon 3 mRNA was particularly strong in cytoplasm of HCC when compared with those of para-cancerous tissues and normal liver tissues. Conclusion: β-catenin gene mutation and overexpression may have a critical role in malignant progression of hepatic carcinogenesis among Chinese people.