beta-catenin mutations are associated with a subset of low-stage hepatocellular carcinoma negative for hepatitis B virus and with favorable prognosis

To better understand the role of beta-catenin mutation in hepatocellular ca rcinoma (HCC), me correlated the gene mutation with hepatitis virus B (HBV) and hepatitis virus C (HCV) status and the clinicopathological features in 366 patients with resected primary unifocal HCC. beta-Catenin mutations me re also analyzed in 55 patients with multifocal HCC (68 tumors). Of the who le series, 57 (13.1%) of 434 tumors examined had beta-catenin mutations, 34 occurred at the serine/threonine residues of the GSK-3 beta region of beta -catenin, Outside the GSK-3 beta phosphorylation site, codons 32 and 34 wer e two mutational hot spots (17 tumors). The non-HBV-related HCC that was pr edominantly HCV related had a higher frequency of mutation (P < 0.00001) an d more frequent mutations at codon 45 than HBV-related HCC, HBV-related HCC had a younger mean age (P < 0.00001), and higher male-to-female ratio (P < 0.003) and positive familial history of HCC (P < 0.014), Among 366 unifoca l HCCs selected for clinicopathological analysis, beta-catenin mutations me re associated with grade I (P = 0.005) and stage I and II HCC (P < 0.0001), and a better 5-year survival rate (P = 0.00003), These findings suggest me chanisms for beta-catenin. mutations differ between HBV-related and non-HBV -related HCCs, and that beta-catenin mutation is a favorable prognostic fac tor related to low stage. beta-Catenin mutation was associated with nuclear expression of the protein (P < 0.00001), but me failed to detect point or large fragment deletion mutation in. 39 HCCs with nuclear beta-catenin expr ession, presumably mild-type protein. HCCs expressing mutant nuclear beta-c atenin. had a better 5-year survival rate (P < 0.007), suggesting that muta nt and wild-type nuclear beta-catenin proteins are not functionally equival ent and deserve more studies for further clarification.