Glypican-3 expression in benign liver tissue with active hepatitis C: implications for the diagnosis of hepatocellular carcinoma

Glypican 3 is an oncofetal antigen that shows great promise as an adjunct to the diagnosis of hepatocellular carcinoma. To investigate whether glypican 3 might also appear in nonneoplastic liver cells, we performed immunostains on 60 biopsies of chronic hepatitis C, 30 with low-grade activity and 30 with high-grade activity. Glypican 3 immunoreactivity was detected in 25 (83.6%) of 30 in the high-grade but in none in the low-grade group. In 20% of the positive cases, glypican 3 produced strong cytoplasmic staining of more than 25% of hepatocytes and could potentially lead to a misdiagnosis of hepatocellular carcinoma. Pathologists should be aware of this phenomenon and exercise caution in interpreting biopsies or other specimens of suspected hepatocellular carcinoma when active necroinflammatory disease is present.