Predicting hepatocellular carcinoma development in advanced fibrosis or cirrhosis due to chronic hepatitis B: The role of glypican-3, heat shock protein 70, CD34, and glutamine synthetase.

BACKGROUND AND AIM: Numerous studies have demonstrated associations between hepatocellular carcinoma (HCC)-related features and markers such as glypican-3 (GPC3), heat shock protein 70 (HSP70), CD34, and glutamine synthetase (GS). In this study, we aimed to quantify these markers in the tissues of patients with cirrhosis or advanced fibrosis due to chronic hepatitis B (CHB). MATERIALS AND METHODS: A retrospective review was conducted on patients with CHB who developed pathologically confirmed HCC and underwent surgical resection between 2003 and 2013. A total of 24 patients who had paired malignant and surrounding cirrhotic tissue samples were included. Liver tissues were categorized as pre-HCC cirrhotic tissue, peritumoral cirrhotic tissue, and malignant HCC tissue. Non-cirrhotic liver samples from CHB patients served as controls. RESULTS: GPC3 staining was observed to be strong in 80% of HCC tissues and was positive in 70% of cirrhotic tissue surrounding HCC. In cirrhotic tissue 44 months prior to HCC development, 60% of cases were GPC3 positive. In non-cirrhotic chronic viral hepatitis, 20% of cases were GPC3 positive. GPC3, CD34, and GS showed significantly stronger staining in malignant versus control tissue (p<0.05). CD34 showed the highest discriminatory performance for malignant versus cirrhotic tissue (sensitivity=91.7%, specificity=91.7%), while GPC3 had the highest sensitivity (83.4%) in differentiating malignant from non-cirrhotic tissue. CONCLUSION: GPC3 expression may be a predictive marker for HCC development in patients with CHB-related cirrhosis. CD34 also has considerable accuracy in differentiating HCC from cirrhotic and non-cirrhotic tissues, supporting a role for use in HCC detection.