ORIGINAL ARTICLE: Expression pattern of glypican-3, HSP70, and glutamine synthetase in chronic hepatitis B and hepatocellular carcinoma

Background and aim: The three-panel marker, glypican-3, HSP70 and glutamine synthetase, is helpful for making a diagnosis of early hepatocellular carcinoma. To further characterize the diagnostic values of these three markers, we performed immunostaining studies in non-neoplastic hepatocytes (chronic hepatitis B) and hepatocellular carcinoma. Methods: Immunostaining was performed for all three markers. The cases were 60 needle biopsies of chronic hepatitis B (30 with low-grade activity and 30 with high-grade activity) and 40 hepatocellular carcinomas (HCCs). Results: Glypican-3 staining was detected in only one of the 60 chronic hepatitis B cases, and this case expressed moderate immunoreactivity for glypican-3 and showed high-grade inflammatory activity. HSP70 expression was not observed in any cases. Glutamine synthetase was strongly immunoreactive at peri-venular hepatocytes with cytoplasmic staining in all cases. These findings reflected a normal expression pattern. On the other hand, all three markers were positive in 15 (37.5%) HCCs. At least two of three markers were positive in 26 (65.0%). Moreover, all three markers were negative in 2 (5.0%) HCCs. Conclusions: The combination of these three markers is highly specific for detecting hepatocellular carcinoma. However, caution should be exercised because non-neoplastic hepatocytes in chronic hepatitis B with high necro-inflammatory activity tend to show focal positivity for glypican-3. Also we emphasize that all three markers can show negative immunoreactivity in HCC.