title: 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.
abstract: Glypican-3 (GPC-3), a membrane-anchored heparin sulfate proteoglycan, has been shown to be expressed in approximately 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 > or =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.
authors.affiliation: Division of Anatomic Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA. nassar.aziza@mayo.edu
authors.forename: A
authors.initials: A
authors.lastname: Nassar
authors.forename: C
authors.initials: C
authors.lastname: Cohen
authors.forename: M T
authors.initials: MT
authors.lastname: Siddiqui
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D044963:Biopsy, Fine-Needle; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000378:metabolism; D003937:Diagnosis, Differential; D053673:Glypicans / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051034:Inhibitor of Apoptosis Proteins; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D011230:Precancerous Conditions / Q000175:diagnosis* / Q000378:metabolism; D012680:Sensitivity and Specificity; D000077022:Survivin
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; C105937:GPC3 protein, human; D053673:Glypicans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D000077022:Survivin