title: Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer.
abstract: Primary liver cancers are classified into three types based on their morphology and cytogenetic characteristics hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular and cholangiocarcinoma (CHC). It is often difficult to distinguish these liver tumors. Glypican-3 (GPC3) is serological and histochemical marker of hepatocellular carcinoma. In order to separate these three types of liver cancers, we analyzed the GPC3 expression in 85 liver resection specimens, including 46 HCCs, 28 ICCs and 11 CHCs. GPC3 immunohistochemical staining was used to distinguish HCC from ICC by comparing with the conventional biomarker, alpha-fetoprotein (AFP). The immunostaining of GPC3 was identified in 78.3% (36/46) of HCCs, 60% (9/15) of well differentiated, 88.9% (16/18) of moderately differentiated and 84.6% (11/13) of poorly differentiated HCCs. It was negative in the ICCs. We confirmed that GPC3 expression is specific to HCC component (8/11, 72.7%) but few samples also showed weakly in ICC component (2/11, 18.2%) of CHC sections among 11 cases compared with HCC biomarkers including AFP and hepatocyto paraffin 1 (HepPar1), and ICC biomarkers cytokeratin (CK) 7 and CK19. Three cases in which the macroscopic features resembled ICC did not express GPC3 even in the pathological HCC component. Most (10/11, 91%) of the pathological cholangiocarcinoma components in CHC showed positive staining for CK7 and CK19. The results of this study suggest that GPC3 is a biomarker that is sensitive and specific to HCC component of CHC, and CK7 and CK19 are markers for pathological cholangiocarcinoma component of CHC.
authors.affiliation: National Cancer Center Hospital East, Kashiwa, 277-8577 Chiba, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Shirakawa
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Kuronuma
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Nishimura
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hasebe
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakano
authors.forename: Naoto
authors.initials: N
authors.lastname: Gotohda
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Takahashi
authors.forename: Toshio
authors.initials: T
authors.lastname: Nakagohri
authors.forename: Masaru
authors.initials: M
authors.lastname: Konishi
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Kobayashi
authors.forename: Taira
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nakatsura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000378:metabolism / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology; D018281:Cholangiocarcinoma / Q000378:metabolism* / Q000473:pathology; D005260:Female; D053673:Glypicans / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged
chemical_list: D014408:Biomarkers, Tumor; C105937:GPC3 protein, human; D053673:Glypicans