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

Jpn J Cancer Res. 1999 Dec;90(12):1301-9. doi: 10.1111/j.1349-7006.1999.tb00712.x.

Abstract

A study was conducted to clarify the contribution of beta-catenin accumulation and mutation of the beta-catenin gene to hepatocarcinogenesis. Beta-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 beta-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 beta-catenin gene can lead to beta-catenin accumulation, although other mechanisms of accumulation may also operate in HCC, and (2) beta-catenin accumulation and mutation of the beta-catenin gene are not early events in hepatocarcinogenesis, and may be associated with the malignant progression of HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism*
  • Exons / genetics*
  • Female
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Mutation*
  • Trans-Activators*
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Trans-Activators
  • beta Catenin