title: The glypican 3 oncofetal protein is a promising diagnostic marker for hepatocellular carcinoma.
abstract: Expression profiling of hepatocellular carcinoma has demonstrated that glypican 3 (GPC3), a heparan sulfate proteoglycan anchored to the membrane, is expressed at a markedly elevated level in hepatocellular carcinoma. In this paper, two monoclonal antibodies against GPC3, GPC3-C02 and A1836A, were confirmed to specifically recognize GPC3 molecule in cells from hepatocellular carcinoma and hepatoblastoma cell lines by immunoblotting, and both were confirmed to recognize different epitopes of the GPC3 molecule by epitope mapping. Then, we evaluated the feasibility of GPC3-immunohistochemistry in the pathological diagnosis of benign and malignant hepatocellular lesions by applying these monoclonal antibodies to formalin-fixed and paraffin-embedded specimens. The immunoreactivity turned out to be identical in the two monoclonal antibodies and was thus confirmed to represent the actual expression of the GPC3 molecule. The expression was observed in the fetal liver, but not in normal adult liver, liver cirrhosis or hepatitis except for a tiny focus of a regenerative nodule of fulminant hepatitis. Diffusely positive staining of GPC3 was observed in malignant hepatocytes in hepatoblastomas and in hepatocellular carcinomas (47/56, 84%). GPC3 expression was independent of the differentiation and size of the hepatocellular carcinoma. On the other hand, there was only weak and focal staining in low-grade (2/8) and high-grade dysplastic nodules (6/8). GPC3 immunoreactivity was detected in only one of 23 metastatic lesions of colorectal carcinoma, and its expression was entirely absent in the liver cell adenoma (0/7), carcinoid tumor (0/1), and cholangiocellular carcinoma (0/16). When compared with immunohistochemistry of hepatocyte antigen and alpha-fetoprotein, GPC3-immunohistochemistry was significantly much more specific and sensitive for hepatocellular carcinomas. Thus, GPC3 was confirmed to be one of the oncofetal proteins now attracting attention for their promise both as markers of hepatocellular carcinoma in routine histological examination and as targets in monoclonal antibody-based hepatocellular carcinoma therapy.
authors.affiliation: Department of Pathology, Graduate School of Medicine, University of Tokyo, Hongo, Tokyo, Japan. yamauchi-tky@umin.ac.jp
authors.forename: Naoko
authors.initials: N
authors.lastname: Yamauchi
authors.forename: Akira
authors.initials: A
authors.lastname: Watanabe
authors.forename: Michiyo
authors.initials: M
authors.lastname: Hishinuma
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Ohashi
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Midorikawa
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Morishita
authors.forename: Toshiro
authors.initials: T
authors.lastname: Niki
authors.forename: Junji
authors.initials: J
authors.lastname: Shibahara
authors.forename: Masaya
authors.initials: M
authors.lastname: Mori
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Makuuchi
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Hippo
authors.forename: Tatsuhiko
authors.initials: T
authors.lastname: Kodama
authors.forename: Hiroko
authors.initials: H
authors.lastname: Iwanari
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Masashi
authors.initials: M
authors.lastname: Fukayama
mesh_terms: D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000276:immunology; D000951:Antigens, Neoplasm / Q000276:immunology / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000175:diagnosis* / Q000378:metabolism; D045744:Cell Line, Tumor; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans / Q000276:immunology / Q000378:metabolism*; D018197:Hepatoblastoma / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008099:Liver / Q000196:embryology / Q000378:metabolism; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D053673:Glypicans; D019812:Heparan Sulfate Proteoglycans