Expression of Glypican-3(gpc-3) and 8-Hydroxydeoxyguanosine (8-Ohdg) in Chronic Hepatitis C and Relationship With Hepatocellular Carcinoma

Abstract

Background: In Egypt, hepatocellular carcinoma (HCC) is the second most common cancer in men and the 6th most common cancer in women. Egypt has the highest prevalence of HCV in the world and the prevalence of HCC is increasing in the last years. Glypican-3 (GPC-3), a member of heparin sulfate proteoglycans, plays a role in cell growth, differentiation, and migration. 8-Hydroxydeoxyguanosine (8-OHdG) is an oxidatively modified promutagenic DNA that is produced by oxygen radicals and is recognized as a useful marker in estimating DNA damage induced by oxidative stress. The aim: This study was conducted to evaluate glypican-3 (GPC-3) and 8-hydroxydeoxyguanosine (8-OHdG) expression in chronic hepatitis C and hepatocellular carcinoma as predictive markers for hepatocellular carcinoma. Methods: 75 cases (50 cases of chronic hepatitis C and 25 of hepatocellular carcinoma) were examined immunohistochemically using antibodies against Glypican-3 (GPC-3) and 8-Hydroxydeoxyguanosine (8-OHdG). Results: Glypican-3 expression was observed in 18 % of cases of chronic hepatitis C, all positive cases were in the high grade, while none of low grade chronic hepatitis cases showed glypican-3 positivity. Glypican-3 expression was observed in 88% of cases of HCC. High 8-OHdG index was observed in 72.4% of cases of low grade chronic hepatitis and 95.2% of cases of high grade chronic hepatitis, while low index was observed in 27.6% of low grade chronic hepatitis and in 4.8% of cases of high grade chronic hepatitis. There was a statistically significant difference in 8-OHdG expression between low and high grade chronic hepatitis (P=0.05). There was no statistically significant difference in glypican-3 and 8-OHdG expression between different grades of HCC. Conclusion: Glypican-3 was expressed in 18% of cases of chronic hepatitis C, 35.1% of cirrhosis and 36.4% of cirrhosis adjacent to hepatocellular carcinoma. Our results suggest that GPC-3 may be considered as an early marker of liver carcinogenesis. 8-OHdG was observed in all cases of chronic hepatitis C, with high labeling index in 82% of cases and low index in 18% of cases. Our study showed high labeling index of 8-OHdG in 52% of cases of HCC. These results indicate that oxidative DNA damage is common in livers with chronic injury suggesting a possible link between chronic inflammation and hepatocarcinogenesis.