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

Abstract

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.