Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer

Glypican-3 is a useful diagnostic marker for a component of hepatocellular carcinoma in human liver cancer
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DOI:
10.3892/ijo_00000190
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发表时间:
2009-03-01
影响因子:
5.2
通讯作者:
Nakatsura, Tetsuya
Nakatsura, Tetsuya
中科院分区:
医学2区
文献类型:
--
作者:
Shirakawa, Hirofumi;Kuronuma, Toshimitsu;Nakatsura, Tetsuya

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根据肝细胞癌的形态和细胞遗传学特征,将其分为肝细胞癌、肝内胆管细胞癌和肝细胞胆管联合癌三种类型。通常很难区分这些肝脏肿瘤。GPC3是肝细胞癌的血清学和组织化学标志物。为了区分这三种类型的肝癌,我们分析了85例肝切除标本中GPC3的表达,其中46例肝细胞癌,28例肝细胞癌和11例肝细胞癌。用GPC3免疫组织化学染色与常规生物标记物甲胎蛋白(AFP)进行比较,以区分肝细胞癌和肝细胞癌。GPC3在78.3%(36/46)、60%(9/15)、88.9%(16/18)、84.6%(11/13)的低分化癌中阳性表达。ICCs中为阴性。我们证实GPC3在11例肝细胞癌组织中的表达是特异的(8/11,72.7%),但在11例CHC切片中,与AFP、肝细胞石蜡切片1(HepPar1)、ICC细胞角蛋白(CK)7和CK19相比,很少有标本在ICC组织中表达弱(2/11,18.2%)。3例大体特征与ICC相似的病例甚至在病理肝细胞癌组织中均未表达GPC3。CK7和CK19在CHC病理胆管细胞癌组织中的阳性表达占91%(10/11)。本研究结果提示,GPC3是对CHC中肝细胞癌成分敏感和特异的生物标志物,CK7和CK19是CHC中病理性胆管细胞癌成分的标志物。
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.