Uthamalingam Preithy, Das Ashim, Behra Arunanshu, Kalra Naveen, Chawla Yogesh
Department of Histopathology, PGIMER, Chandigarh, India.
Department of Surgery, PGIMER, Chandigarh, India.
J Clin Exp Hepatol. 2018 Jun;8(2):173-180. doi: 10.1016/j.jceh.2017.09.005. Epub 2017 Oct 7.
Histopathological distinction of various nodular lesions in liver with sufficient sensitivity and specificity is a challenge even in an expert set up. The panel of immunohistochemical markers composed of glutamine synthetase (GS), Glypican3 (GPC3) and heat shock protein 70 (HSP70) was recommended by the International Consensus Group for Hepatocellular Neoplasia group for the differentiation of high grade dysplastic nodule and early hepatocellular carcinoma (HCC). The panel has been extensively validated in the western population. This study aims to test this panel on Indian population on resected, explanted and autopsy cirrhotic and non-cirrhotic liver specimens of HCC.
This study was conducted on 39 such liver specimens (12 cirrhotic, 12 pre-cirrhotic and 11 non-cirrhotic, non-fibrotic livers), including 35 cases of HCC over a period of 12 years. Immunohistochemistry was performed with antibodies against GS, GPC3 and HSP70 on the sections containing both malignant and dysplastic nodules.
The diagnostic yield depended upon the nature of background liver pathology and was found to be high for only those HCCs arising in cirrhotic background, when positivity of any two markers was taken to be in favor of HCC (sensitivity-58.33%; specificity-100%). GS had a sensitivity and Negative predictive value of 100% for HCCs arising in cirrhotic livers.
Strong positivity for GS is a highly sensitive marker for HCC in a cirrhotic background regardless of the differentiation of the tumor in Indian population. This may be due to preferential activation of Wnt pathway in Indian patients with cirrhosis. The sensitivity of the panel was too low for detecting HCCs arising in non-cirrhotic livers, even in the pre-cirrhotic chronically inflamed livers, even though the specificity was high. GPC3 and HSP70 appear to be useful as individual markers for HCCs arising in non-cirrhotic livers.
即便在专业机构中，要以足够的敏感性和特异性对肝脏中的各种结节性病变进行组织病理学区分也是一项挑战。国际肝细胞肿瘤共识小组推荐使用由谷氨酰胺合成酶（GS）、磷脂酰肌醇蛋白聚糖3（GPC3）和热休克蛋白70（HSP70）组成的免疫组化标志物组合，用于鉴别高级别发育异常结节和早期肝细胞癌（HCC）。该标志物组合已在西方人群中得到广泛验证。本研究旨在对印度人群中切除的、移植的以及尸检的肝硬化和非肝硬化肝脏标本中的HCC进行该标志物组合的检测。
本研究在12年期间对39份此类肝脏标本（12份肝硬化标本、12份肝硬化前期标本和11份非肝硬化、无纤维化肝脏标本）进行，其中包括35例HCC病例。在包含恶性结节和发育异常结节的切片上，使用抗GS、GPC3和HSP70的抗体进行免疫组化。
诊断率取决于背景肝脏病理的性质，发现仅对于那些在肝硬化背景下发生的HCC，当任何两种标志物呈阳性被判定为支持HCC时，诊断率较高（敏感性 - 58.33%；特异性 - 100%）。对于在肝硬化肝脏中发生的HCC，GS的敏感性和阴性预测值均为100%。
在印度人群中，无论肿瘤的分化程度如何，GS的强阳性是肝硬化背景下HCC的高敏感标志物。这可能是由于印度肝硬化患者中Wnt通路的优先激活。该标志物组合对于检测非肝硬化肝脏中发生的HCC，甚至是肝硬化前期慢性炎症肝脏中的HCC，敏感性都过低，尽管特异性较高。GPC3和HSP70似乎是检测非肝硬化肝脏中发生的HCC的有用的单个标志物。
