Utility of glypican‐3 and survivin in differentiating hepatocellular carcinoma from benign and preneoplastic hepatic lesions and metastatic carcinomas in liver fine‐needle aspiration biopsies

Glypican‐3 (GPC‐3), a membrane‐anchored heparin sulfate proteoglycan, has been shown to be expressed in ～80% of hepatocellular carcinoma (HCC) but not in benign hepatic lesions. Survivin, a novel inhibitor of apoptosis, and a prognostic marker, has also been expressed in HCC. We evaluated these two immunomarkers (GPC‐3 and survivin) in differentiating HCC from benign and preneoplastic hepatic lesions and metastatic carcinomas, comparing them to HepPar‐1 (hepatocyte paraffin‐1) in liver fine‐needle aspiration biopsies (FNAB). Immunohistochemistry for GPC‐3, survivin and HepPar‐1 was performed on 92 FNAB including HCC, hepatic cirrhosis, focal nodular hyperplasia (FNH), hepatic adenoma, dysplastic hepatic nodules and metastatic carcinomas. Immunostaining was scored as positive, if ≥10% of tumor cells stained. GPC‐3 is immunoexpressed in 56.8% of HCC, but not in benign and preneoplastic hepatic lesions, or metastatic carcinomas; whereas survivin is expressed in HCC (86.4%), benign hepatic lesions (85.7%), dysplastic hepatic nodules (100%) and metastatic carcinomas (94.3%). HepPar‐1 is immunoexpressed in HCC (72.7%), benign hepatic lesions (100%), dysplastic nodules (100%) and metastatic carcinomas (2.9%). The sensitivity and specificity of GPC‐3, survivin and HepPar‐1 for detection of HCC are 56.8 and 100%, 86.4 and 6.3%, 72.7 and 70.8%, respectively. GPC‐3 is a reliable and more specific immunohistochemical marker than survivin for the diagnosis of HCC in FNAB. HepPar‐1, although a more sensitive marker than GPC‐3, has a lower specificity for detection of HCC. Our data supports the potentially significant diagnostic utility of GPC‐3 in FNABs in differentiating primary malignant from benign and preneoplastic liver lesions, and metastatic carcinomas. Diagn. Cytopathol. 2009. © 2009 Wiley‐Liss, Inc.