Shafizadeh Nafis, Ferrell Linda D, Kakar Sanjay
Department of Anatomic Pathology, University of California, San Francisco, CA 94121, USA.
Mod Pathol. 2008 Aug;21(8):1011-8. doi: 10.1038/modpathol.2008.85. Epub 2008 Jun 6.
Glypican-3 is a heparin sulfate proteoglycan normally expressed in fetal liver and placenta, but not in normal adult liver. Preliminary studies have shown that glypican-3 can be useful for the diagnosis of hepatocellular carcinoma. We performed immunohistochemistry for glypican-3 on 80 resection cases of hepatocellular lesions to examine the utility of glypican-3 immunohistochemistry in hepatocellular carcinoma at two ends of the differentiation spectrum. Staining was compared to Hep Par 1 in poorly differentiated cases. Glypican-3 was expressed in 46 (79%) hepatocellular carcinomas (56, 83 and 89% of well, moderately and poorly differentiated respectively) and seven (64%) fibrolamellar carcinomas. Of the 16 well differentiated cases, 10 closely resembled adenoma and were diagnosed due to focal abnormalities and/or loss of reticulin. Glypican-3 expression was seen in 50% in this group. Hepatocellular carcinomas arising in cirrhotic liver were more likely to be glypican-3 positive (91 vs 57%, P=0.004). All hepatic adenomas and macroregenerative nodules were negative, and three (43%) high grade dysplastic nodules were positive. Focal staining was seen in regenerative nodules in four (11%) cirrhosis cases. Glypican-3 was significantly more sensitive than Hep Par 1 for diagnosis of poorly differentiated hepatocellular carcinomas (89 vs 63%, P=0.02). The difference was more significant when only cases with diffuse positive staining were considered (83 vs 21%, P<0.001). In conclusion, glypican-3 has high sensitivity for the diagnosis of hepatocellular carcinoma, but is less sensitive in the extremely well differentiated hepatocellular carcinoma and fibrolamellar variant of hepatocellular carcinoma. Caution should be exercised in using glypican-3 in biopsy specimens as cirrhotic nodules can show strong expression. Glypican-3 can be especially useful in the identification of poorly differentiated hepatocellular carcinoma as it has higher sensitivity compared to Hep Par 1.
磷脂酰肌醇蛋白聚糖-3是一种硫酸乙酰肝素蛋白聚糖，正常情况下在胎儿肝脏和胎盘中表达，但在正常成人肝脏中不表达。初步研究表明，磷脂酰肌醇蛋白聚糖-3可用于肝细胞癌的诊断。我们对80例肝细胞病变切除病例进行了磷脂酰肌醇蛋白聚糖-3免疫组化，以研究磷脂酰肌醇蛋白聚糖-3免疫组化在分化谱两端的肝细胞癌中的应用价值。在低分化病例中，将染色结果与肝细胞石蜡1（Hep Par 1）进行比较。磷脂酰肌醇蛋白聚糖-3在46例（79%）肝细胞癌中表达（高分化、中分化和低分化分别为56%、83%和89%），在7例（64%）纤维板层癌中表达。在16例高分化病例中，10例与腺瘤极为相似，因局灶性异常和/或网状纤维丢失而被诊断。该组中50%可见磷脂酰肌醇蛋白聚糖-3表达。肝硬化肝脏中发生的肝细胞癌更可能为磷脂酰肌醇蛋白聚糖-3阳性（91%对57%，P=0.004）。所有肝腺瘤和大再生结节均为阴性，3例（43%）高级别发育异常结节为阳性。在4例（11%）肝硬化病例的再生结节中可见局灶性染色。在诊断低分化肝细胞癌方面，磷脂酰肌醇蛋白聚糖-3比肝细胞石蜡1（Hep Par 1）显著更敏感（89%对63%，P=0.02）。仅考虑弥漫性阳性染色病例时，差异更显著（83%对21%，P<0.001）。总之，磷脂酰肌醇蛋白聚糖-3对肝细胞癌的诊断具有高敏感性，但在高分化肝细胞癌和肝细胞癌的纤维板层变异型中敏感性较低。在活检标本中使用磷脂酰肌醇蛋白聚糖-3时应谨慎，因为肝硬化结节可显示强表达。磷脂酰肌醇蛋白聚糖-3在识别低分化肝细胞癌方面可能特别有用，因为与肝细胞石蜡1（Hep Par 1）相比，它具有更高的敏感性。
