Shirakawa Hirofumi, Kuronuma Toshimitsu, Nishimura Yoshiko, Hasebe Takahiro, Nakano Masayuki, Gotohda Naoto, Takahashi Shinichiro, Nakagohri Toshio, Konishi Masaru, Kobayashi Nobuaki, Kinoshita Taira, Nakatsura Tetsuya
National Cancer Center Hospital East, Kashiwa, 277-8577 Chiba, Japan.
Int J Oncol. 2009 Mar;34(3):649-56. doi: 10.3892/ijo_00000190.
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.
肝细胞癌（HCC）、肝内胆管癌（ICC）和肝细胞胆管癌（CHC）。区分这些肝脏肿瘤通常很困难。磷脂酰肌醇蛋白聚糖-3（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例肝切除标本中的GPC3表达情况，其中包括46例HCC、28例ICC和11例CHC。通过与传统生物标志物甲胎蛋白（AFP）比较，采用GPC3免疫组化染色来区分HCC和ICC。在46例HCC中，78.3%（36/46）检测到GPC3免疫染色，其中高分化HCC的阳性率为60%（9/15），中分化为88.9%（16/18），低分化为84.6%（11/13）。在ICC中呈阴性。与包括AFP和肝细胞石蜡1（HepPar1）的HCC生物标志物以及ICC生物标志物细胞角蛋白（CK）7和CK19相比，我们证实GPC3表达对CHC中的HCC成分具有特异性（8/11，72.7%），但在11例CHC切片的ICC成分中也有少数样本呈弱阳性（2/11，18.2%）。3例宏观特征类似ICC的病例即使在病理HCC成分中也未表达GPC3。CHC中大多数（10/11，91%）病理胆管癌成分对CK7和CK19呈阳性染色。本研究结果表明，GPC3是对CHC中HCC成分敏感且特异的生物标志物，CK7和CK19是CHC中病理胆管癌成分的标志物。
