Branched chain in situ hybridization for albumin as a marker of hepatocellular differentiation: evaluation of manual and automated in situ hybridization platforms.
Branched chain in situ hybridization for albumin as a marker of hepatocellular differentiation: evaluation of manual and automated in situ hybridization platforms.
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DOI：
10.1097/pas.0000000000000343
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发表时间：
2015-01
期刊：
影响因子：
--
通讯作者：
Deshpande V
中科院分区：
文献类型：
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作者：
Shahid M;Mubeen A;Tse J;Kakar S;Bateman AC;Borger D;Rivera MN;Ting DT;Deshpande V
白蛋白被广泛认为是肝细胞癌的高度敏感和特异的标志物，但由于缺乏强大的平台，目前诊断实验室无法获得白蛋白。在之前的一项研究中，我们使用一种新的支链RNA原位杂交(ISH)平台在大多数肝内胆管细胞癌中检测到白蛋白mRNA。我们现在探讨白蛋白ISH作为肝细胞癌分化标志物的作用，并与Hep PAR 1和精氨酸酶-1比较其敏感性。我们评估了93例肝癌及其类似物，包括胃肠道神经内分泌肿瘤(n=31)、胰腺神经内分泌肿瘤(n=163)、黑色素瘤(n=15)和胆囊癌(n=34)。进行白蛋白原位杂交和Hep-PAR-1、Arg-1免疫组织化学染色。来自我们的档案中的五个以前没有特征性的肝脏肿瘤也被评估。对59例肝内胆管细胞癌进行精氨酸酶-1免疫组织化学染色。此外，在人工平台上评估的43种氟氯烃也在自动化仪器上进行了检查。55%为中分化，39%为低分化。ISH对白蛋白的敏感性为99%，93例肝细胞癌中92例白蛋白染色阳性。免疫组织化学检测Hep Par1和Arg-1的敏感性分别为84%和83%。白蛋白对低分化肝癌的敏感性为99%，对精氨酸酶-1和HEp-PAR-1的敏感性分别为71%和%。使用ISH平台，97%的肝癌细胞白蛋白阳性；50%的肿瘤细胞白蛋白阳性，而Hep PAR 1和精氨酸酶-1免疫组织化学分别为76%和70%。在5例无特征性的肿瘤中，有3例白蛋白ISH阳性。自动化白蛋白ISH平台的表现与手动格式相同，在所有43例在两个平台上进行测试的病例中，50%的肿瘤细胞中有白蛋白反应。所有非肝癌患者的白蛋白均为阴性。59例肝内胆管细胞癌均为精氨酸酶-1阴性。在人工和自动模式下进行的支链ISH是一种检测白蛋白的可靠方法，其对低分化肝癌的敏感性优于精氨酸酶-1和Hep PAR-1。当与精氨酸酶-1一起解释时，白蛋白ISH提供了高水平的敏感性和特异性。
Albumin, widely recognized as a highly sensitive and specific marker of hepatocellular carcinoma (HCC) is currently unavailable in the diagnostic laboratory because of the lack of a robust platform. In a prior study we detected albumin mRNA in the majority of intrahepatic cholangiocarcinomas using a novel branched chain RNA in situ hybridization (ISH) platform. We now explore the utility of albumin ISH as a marker of hepatocellular differentiation in hepatocellular carcinomas, and compare its sensitivity with Hep Par 1 and Arginase-1. We evaluated 93 HCCs and its mimics including neuroendocrine tumors of the gastrointestinal tract (n= 31), neuroendocrine tumors of the pancreas (n= 163), melanoma (n= 15), and gallbladder carcinoma (n=34). We performed ISH for albumin and immunohistochemistry for Hep Par 1 and Arginase-1. Five previously uncharacterized hepatic neoplasms from our files were also evaluated. Immunohistochemistry for Arginase-1 was performed on 59 intrahepatic cholangiocarcinomas. In addition, 43 HCCs evaluated on the manual platform, were also examined on the automated instrument. 55% of HCCs were moderately differentiated and 39% poorly differentiated. The sensitivity of ISH for Albumin was 99% with 92 of 93 of HCCs staining positive for albumin. In contrast to ISH, the sensitivity of immunohistochemistry for Hep Par1 and Arginase-1 was 84 % and 83 %, respectively. The sensitivity of albumin for poorly differentiated HCCs was 99%, while that for Arginase-1 and Hep Par 1 was 71% and 64%, respectively. 97% of the HCCs showed albumin positivity in >50% of tumor cells using the ISH platform, as compared to 76% and 70% for Hep Par 1 and Arginase-1 immunohistochemistry, respectively. 3 of the 5 previously uncharacterized neoplasms were positive for albumin ISH. Automated albumin ISH platform performed equivalently to the manual format, with albumin reactivity in >50% of tumor cells in all 43 cases that were tested on both platforms. All non- HCCs were negative for albumin. All 59 intrahepatic cholangiocarcinomas were negative for Arginase-1. Branched chain ISH performed on manual and automated mode is a robust assay for detecting albumin with sensitivity for poorly differentiated HCC superior to Arginase-1 and Hep Par 1. When interpreted in conjunction with Arginase-1, albumin ISH offers a high level of sensitivity as well as specificity.