Beta-catenin accumulation and mutation of exon 3 of the beta-catenin gene in hepatocellular carcinoma.
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.
Kondo
Y
Y
Pathology Division, National Cancer Center Research Institute, Tokyo.
Kanai
Y
Y
Sakamoto
M
M
Genda
T
T
Mizokami
M
M
Ueda
R
R
Hirohashi
S
S
D000328:Adult; D000368:Aged; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism*; D005091:Exons / Q000235:genetics*; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015534:Trans-Activators; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin