β‐Catenin Accumulation and Mutation of Exon 3 of the β‐Catenin Gene in Hepatocellular Carcinoma

Abstract
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 (PPcatenin 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.