Utility of an Immunohistochemical Panel Consisting of Glypican-3, Heat-shock Protein-70, and Glutamine Synthetase in the Distinction of Low-grade Hepatocellular Carcinoma From Hepatocellular Adenoma

Background: The pathologic distinction between hepatocellular carcinoma (HCC) and hepatocellular adenoma (HCA) is sometimes problematic due to histologic overlap between the 2 entities, a problem amplified on small biopsy specimens. Several recently characterized immunohistochemical markers such as glypican-3 (GPC-3), heat-shock protein-70 (HSP-70), and glutamine synthetase (GS) help distinguish dysplastic nodules from HCC. The utility of this panel in the distinction of low-grade hepatocellular carcinoma (LG-HCC) from HCA has not been fully described. Objective: To determine whether the above markers are useful in the distinction of HCCs from HCAs. Design: Tissue microarrays were constructed with 30 LG-HCCs and 18 HCAs. The arrays were stained with the above markers and analyzed with respect to amount and pattern of staining. GPC-3 and HSP-70 were considered positive when 10% of tumor cells showed immunoreactivity. GS was considered positive when 50% of tumor cells showed immunoreactivity. Results: GPC-3 was positive in 13 of 30 LG-HCCs and 0 of 18 adenomas. The sensitivity was 43% and the specificity was 100%. HSP-70 was positive in 14 of 30 LG-HCCs and 0 of 18 adenomas. The sensitivity was 46% and the specificity was 100%. GS was positive in 24 of 30 LG-HCCs and 9 of 18 adenomas. The sensitivity was 80% and the specificity was 50%. Conclusions: GPC-3 and HSP-70 are helpful in separating carcinomas from adenomas. GS is not useful in this clinical context.