Tissue expression of β-catenin and E- and N-cadherins in chronic hepatitis C and hepatocellular carcinoma

Introduction: The role of Wnt/β-catenin signaling 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-and N-cadherins and HCV proteins (C, NS3, NS5A) in long-lasting (≥ 20 years) chronic hepatitis C (CH-C) (n = 54), hepatocellular carcinoma (HCC) (n = 61), and control liver samples (n = 8).Results: Typical membranous expression of β-catenin in the control liver was higher than in the CH-C and HCC (p = 0.06).The mean β-catenin tissue expression in CH-C was similar to controls, and significantly higher than that of HCC (p = 0.005).E-cadherin expression was lower in CH-C than in the control (p = 0.045) and HCC (p < 0.001).In HCC both β-catenin and E-cadherin expressions were significantly lower in comparison to controls (p = 0.02, p = 0.001, respectively).Positive correlations were found between β-catenin and E-cadherin (in CH-C and HCC), β-catenin and N-cadherin (HCC), E-and N-cadherins expressions (HCC) (p < 0.05 in all cases).In CH-C the positive correlation was demonstrated between NS5A protein and β-catenin, and between the all HCV proteins (C, NS3, NS5A) and E-cadherin expression (p < 0.05 in all cases).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.