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Cancer. 2007 Oct 25;111(5):316-22.

Glypican-3 immunocytochemistry in liver fine-needle aspirates : a novel stain to assist in the differentiation of benign and malignant liver lesions.

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  • 1Department of Pathology, University of Vermont, Burlington, Vermont, USA.



Glypican-3 (GPC3) is a heparan sulfate proteoglycan which is elevated in the serum of patients with hepatocellular carcinoma (HCC), but not in healthy blood donors, or patients with benign liver disease. GPC3 immunohistochemistry (IHC) is a promising marker of HCC in surgical pathology. This study explores the value of GPC3 expression in liver fine-needle aspirates (FNAs) by immunocytochemistry (ICC), and compares its sensitivity and staining intensity with that of IHC.


Archival cytologic material in hepatic FNAs from 20 patients with HCC, 20 patients with metastatic tumors, and 20 patients with benign lesions, were studied. Correlating surgical specimens and/or cell blocks were available for GPC-3 IHC in 16 patients with HCC. All slides were stained with GPC3-1G12 antibody with appropriate positive and negative controls. Staining intensity was graded as 0, no staining; 1, weak cytoplasmic staining; 2, moderate cytoplasmic staining; 3, strong cytoplasmic staining with membranous accentuation. Grades 0 and 1 were regarded as negative; grades 2 and 3 were considered positive for GPC3.


In the HCC group, positive staining was found in 18/20 (90%) samples. In contrast, GPC3 ICC of 20/20 (100%) metastatic tumors and 20/20 (100%) benign cases displayed negative staining, no cases showing moderate or strong expression. The sensitivity and specificity of GPC3 in HCC ICC were 90% and 100% respectively. The surgical sections and cell blocks of HCC demonstrated positive staining less frequently, in 11/16 (68.8%) cases, with 12/16 (75%) correlation with ICC.


Results indicated positive staining for GPC3 as defined in 90% of liver FNAs from HCC patients. All metastatic tumors and benign aspirates studied were negative for GPC3. ICC was superior to IHC in 25% of cases. This pilot study supports the diagnostic utility of GPC3 in hepatic FNAs to aid in distinction of HCC from metastatic tumors and benign liver lesions.

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