Immunohistochemical expression of CD95 (Fas), c-myc and epidermal growth factor receptor in hepatitis C virus infection, cirrhotic liver disease and hepatocellular carcinoma

Abstract

Gene product expression in normal and chronic hepatitis C virus infection was determined in an attempt to improve our understanding of the molecular events leading to the development of cirrhosis and liver carcinoma. Activation of CD95 (Fas) causes apoptosis of cells and liver failure in mice and has been associated with human liver disorders. c-myc is involved in cell proliferation and EGFR in regeneration of cells. The material of the current study included 50 cases of chronic hepatitis C (CHC) (and negative hepatitis B virus infection), 29 cases of liver cirrhosis and HCV (LC), and 19 cases of hepatocellular carcinoma and HCV (HCC) admitted to the Theodor Bilharz Research Institute (TBRI) during the years 2003-2004. Ten wedge liver biopsies - taken during laparoscopic cholecystectomy - were included in the study as normal controls. Laboratory investigations, including liver function tests, serological markers for viral hepatitis and serum alpha fetoprotein level (α-FP), were determined for all cases. Histopathological study and immunohistochemistry using monoclonal antibodies for CD95, c-myc and EGFR were also done. In CHC cases, the histological activity index (HAI) revealed more expression of Fas antigen in liver tissues with active inflammation than in those without active inflammation (p<0.01). EGFR and c-myc act synergistically in liver tumorigenesis. Upregulation of Fas in chronic hepatitis C infection and of c-myc & EGFR in malignant transformation was concluded from this study. c-myc expression may obstruct the induction of apoptosis of HCC cells and lead to uncontrolled cell growth. © 2006 The Authors.