Introduction: The role of the Wnt/β-catenin signalling pathway in HCV-associated hepatocellular carcinogenesis is still unknown.
Material and methods: This study aimed to perform quantitative analysis of immuno- and hybridocytochemical expression of β-catenin, E-cadherin and N-cadherin and HCV proteins (C, NS3, NS5A) in long-term (≥ 20 years) chronic hepatitis C (CH-C) (n = 54), hepatocellular carcinoma (HCC) (n = 61) and control liver (n = 8).
Results: Typical membranous expression of β-catenin in the control liver was significantly higher than in the CH-C and HCC groups. The mean β-catenin tissue expression in CH-C was similar to the control group, and significantly higher than that of HCC. E-cadherin expression was lower in CH-C than in the control and HCC. In HCC expression of both β-catenin and E-cadherin was significantly lower in comparison to controls. Positive correlations were found between β-catenin and E-cadherin (in CH-C and HCC), β-catenin and N-cadherin (HCC), and E- and N-cadherin expression (HCC). The altered liver expression of β-catenin, E and/or N-cadherin did not correlate with any clinicopathological characteristics in the examined groups. In CH-C a positive correlation was demonstrated between NS5A and β-catenin, and between all HCV proteins (C, NS3, NS5A) and E-cadherin expression.
Conclusions: Alterations in cellular locations of β-catenin and E-cadherin in CH-C and HCC pointed to structural disturbances in intercellular junctions in the livers and presence of the transcriptionally inactive form of β-catenin. The reduced expression of E-cadherin in long-lasting CH-C may represent an early indicator of the epithelial-mesenchymal transition. The most important role in modulation of the Wnt/β-catenin pathway in vivo is probably played by the NS5A viral protein.