β-catenin accumulation and mutation of exon 3 of the β-catenin gene in hepatocellular carcinoma

A study was conducted to clarify the contribution of β-catenin accumulation and mutation of the β-catenin gene to hepatocarcinogenesis. β-Catenin accumulation was examined immunohistochemically in 38 paired samples of hepatocellular carcinoma (HCC) and corresponding non-cancerous liver tissue. Gene mutation was analyzed by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and direct sequencing using intronic primers encompassing exon 3. Neither accumulation nor mutation was detected in non-cancerous liver tissues that showed no remarkable histological features, chronic hepatitis or liver cirrhosis. Accumulation of β-catenin was seen in the nucleus, cytoplasm or cell membrane in 15 of 38 (39%) HCC samples, and gene mutation was seen in 9 of 38 (24%) HCC samples. Although there was a significant correlation between accumulation and mutation (P < 0.01), six HCCs without mutation also showed accumulation. Samples of early HCC showed neither accumulation nor mutation, and accumulation and mutation were each correlated significantly with portal vein tumor involvement (P < 0.05). The present results indicate that (1) mutation of exon 3 of the β-catenin gene can lead to β-catenin accumulation, although other mechanisms of accumulation may also operate in HCC, and (2) β-catenin accumulation and mutation of the β-catenin gene are not early events in hepatocarcinogenesis, and may be associated with the malignant progression of HCC.