HCCs with extensive methylation harbor frequent beta-catenin mutations, whereas HCCs with high levels of CIN are associated with p53 mutations, suggesting the presence of two independent pathways for the pathogenesis of HCC.
In addition, this is the first report from Malaysia which shows that there are no mutations at the GSK-3beta consensus phosphorylation sites on beta-catenin gene in all 23 paired HCC and surrounding tissues.
In order to prove this hypothesis, 52 samples from human hepatocellular carcinomas were analysed for the activation of beta-catenin and the expression of GS.
Our present data suggest that beta-catenin plays important roles in promoting tumor progression by stimulating tumor cell proliferation and reducing the activity of cell adhesion systems and is associated with a poor prognosis, especially in patients with poorly differentiated HCCs.
Results of RT-PCR showed the beta-catenin gene exon 3 mRNA Expression Index (EI) of 34 HCCs was higher than that of para-cancerous tissue and normal liver tissue.
These results indicate that the altered expression of beta-catenin in HCC may play an important role in tumor progression by stimulating tumor cell proliferation, and nonnuclear overexpression may have pathologic significance in HCC.