α-Fetoprotein mRNA in situ hybridisation is a highly specific marker of hepatocellular carcinoma: a multi-centre study.

α-Fetoprotein mRNA in situ hybridisation is a highly specific marker of hepatocellular carcinoma: a multi-centre study.
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甲胎蛋白 mRNA 原位杂交是肝细胞癌的高度特异性标志物:一项多中心研究

DOI:
10.1038/s41416-021-01363-4
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发表时间:
2021-06
影响因子:
8.8
通讯作者:
Yun JP
Yun JP
中科院分区:
医学1区
文献类型:
--
作者:
Lu SX;Huang YH;Liu LL;Zhang CZ;Yang X;Yang YZ;Shao CK;Li JM;Xie D;Zhang X;Jain D;Yun JP

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肝细胞癌的病理诊断在与良性和非肝细胞恶性病变的鉴别方面具有挑战性。本研究旨在探讨甲胎蛋白(α-FetoProtein,AFP)基因RNAScope这一敏感而特异的方法在肝癌诊断中的应用价值。对2216例肝细胞癌、良性肝脏病变和非肝细胞肿瘤患者进行了三个独立的回顾性队列研究。用酶联免疫吸附试验、免疫组织化学和RNAScope检测甲胎蛋白。免疫组织化学方法检测GPC3、肝细胞石蜡-1、精氨酸酶-1蛋白的表达。与IHC相比,AFP RNAScope检测肝癌的灵敏度提高了24.7-32.7%。在两个手术队列中,一组AFP RNAScope和GPC3在区分肝癌和良性肝细胞病变方面的诊断价值最好(AUCRNAScope和0.811),而一组包括AFP RNAScope、GPC3、HepPar-1和Arg-1的组在区分肝癌和非肝细胞恶性肿瘤时的AUC值最高(0.971和0.977)。肝活检队列的结果是相似的,在区分肝细胞癌和良性肝细胞病变时,额外应用AFP RNAScope将灵敏度提高了18%。RNAScope检测到的AFP mRNA对肝细胞恶性肿瘤具有高度的特异性,可作为一种新的肝细胞癌诊断生物标志物。
Pathologic diagnosis of hepatocellular carcinoma (HCC) can be challenging in differentiating from benign and non-hepatocytic malignancy lesions. The aim of this study was to investigate the potential utility of α-fetoprotein (AFP) mRNA RNAscope, a sensitive and specific method, in the diagnosis of HCC. Three independent retrospective cohorts containing 2216 patients with HCC, benign liver lesions, and non-hepatocytic tumours were examined. AFP was detected using ELISA, IHC (Immunohistochemistry), and RNAscope. Glypican3 (GPC3), hepatocyte paraffin-1 (HepPar-1), and arginase-1 (Arg-1) proteins were detected using IHC. AFP RNAscope improved the HCC detection sensitivity by 24.7–32.7% compared with IHC. In two surgical cohorts, a panel of AFP RNAscope and GPC3 provided the best diagnostic value in differentiating HCC from benign hepatocytic lesions (AUC = 0.905 and 0.811), and a panel including AFP RNAscope, GPC3, HepPar-1, and Arg-1 yielded the best AUC (0.971 and 0.977) when distinguishing HCC from non-hepatocytic malignancies. The results from the liver biopsy cohort were similar, and additional application of AFP RNAscope improved the sensitivity by 18% when distinguishing HCC from benign hepatocytic lesions. AFP mRNA detected by RNAscope is highly specific for hepatocytic malignancy and may serve as a novel diagnostic biomarker for HCC.
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