Ordóñez Nelson G
University of Texas, Texas 77030, USA.
Am J Surg Pathol. 2003 Aug;27(8):1031-51. doi: 10.1097/00000478-200308000-00001.
A large number of immunohistochemical markers that can facilitate the distinction between epithelioid pleural mesotheliomas and pulmonary peripheral adenocarcinomas have recently become available. The aim of this study is to compare the value of these new markers with others that are already commonly used for this purpose and to determine which are, at present, the best for discriminating between these malignancies. Sixty epithelioid mesotheliomas and 50 lung adenocarcinomas were investigated for expression of the following markers: calretinin, cytokeratin 5/6, WT1, thrombomodulin, mesothelin, CD44S, HBME-1, N-cadherin, E-cadherin, MOC-31, thyroid transcription factor-1 (TTF-1), BG-8 (Lewisy), carcinoembryonic antigen (CEA), Ber-EP4, B72.3 (TAG-72), leu-M1 (CD15), CA19-9, epithelial membrane antigen (EMA), and vimentin. All (100%) of the mesotheliomas reacted for calretinin, cytokeratin 5/6, and mesothelin, 93% for WT1, 93% for EMA, 85% for HBME-1, 77% for thrombomodulin; 73% for CD44S, 73% for N-cadherin, 55% for vimentin, 40% for E-cadherin, 18% for Ber-EP4, 8% for MOC-31, 7% for BG-8, and none for CEA, B72.3, leu-M1, TTF-1, or CA19-9. Of the adenocarcinomas, 100% were positive for MOC-31, Ber-EP4, and EMA, 96% for BG-8, 88% for CEA, 88% for E-cadherin, 84% for B72.3, 74% for TTF-1, 72% for leu-M1, 68% for HBME-1, 48% for CD44S, 48% for CA19-9, 38% for mesothelin, 38% for vimentin, 30% for N-cadherin, 14% for thrombomodulin, 8% for calretinin, 2% for cytokeratin 5/6, and none for WT1. After analyzing the results, it is concluded that calretinin, cytokeratin 5/6, and WT1 are the best positive markers for differentiating epithelioid malignant mesothelioma from pulmonary adenocarcinoma. The best discriminators among the antibodies considered to be negative markers for mesothelioma are CEA, MOC-31, Ber-EP4, BG-8, and B72.3. A panel of four markers (two positive and two negative) selected based upon availability and which ones yield good staining results in a given laboratory is recommended. Because of their specificity and sensitivity for mesotheliomas, the best combination appears to be calretinin and cytokeratin 5/6 (or WT1) for the positive markers and CEA and MOC-31 (or B72.3, Ber-EP4, or BG-8) for the negative markers. An extensive and detailed review of the literature is also provided.
最近出现了大量有助于区分上皮样胸膜间皮瘤和肺外周腺癌的免疫组化标志物。本研究的目的是比较这些新标志物与其他常用于此目的的标志物的价值，并确定目前哪些标志物最适合区分这些恶性肿瘤。对60例上皮样间皮瘤和50例肺腺癌进行了以下标志物表达情况的研究：钙视网膜蛋白、细胞角蛋白5/6、WT1、血栓调节蛋白、间皮素、CD44S、HBME-1、N-钙黏蛋白、E-钙黏蛋白、MOC-31、甲状腺转录因子-1（TTF-1）、BG-8（Lewis y）、癌胚抗原（CEA）、Ber-EP4、B72.3（TAG-72）、leu-M1（CD15）、CA19-9、上皮膜抗原（EMA）和波形蛋白。所有（100%）间皮瘤对钙视网膜蛋白、细胞角蛋白5/6和间皮素呈阳性反应，93%对WT1呈阳性反应，93%对EMA呈阳性反应，85%对HBME-1呈阳性反应，77%对血栓调节蛋白呈阳性反应；73%对CD44S呈阳性反应，73%对N-钙黏蛋白呈阳性反应，55%对波形蛋白呈阳性反应，40%对E-钙黏蛋白呈阳性反应，18%对Ber-EP4呈阳性反应，8%对MOC-31呈阳性反应，7%对BG-8呈阳性反应，对CEA、B72.3、leu-M1、TTF-1或CA19-9均无阳性反应。在腺癌中，100%对MOC-31、Ber-EP4和EMA呈阳性反应，96%对BG-8呈阳性反应，88%对CEA呈阳性反应，88%对E-钙黏蛋白呈阳性反应，84%对B72.3呈阳性反应，74%对TTF-1呈阳性反应，72%对leu-M1呈阳性反应，68%对HBME-1呈阳性反应，48%对CD44S呈阳性反应，48%对CA19-9呈阳性反应，38%对间皮素呈阳性反应，38%对波形蛋白呈阳性反应，30%对N-钙黏蛋白呈阳性反应，对血栓调节蛋白呈阳性反应的为14%，对钙视网膜蛋白呈阳性反应的为8%，对细胞角蛋白5/6呈阳性反应的为2%，对WT1无阳性反应。分析结果后得出结论，钙视网膜蛋白、细胞角蛋白5/6和WT1是区分上皮样恶性间皮瘤和肺腺癌的最佳阳性标志物。在被认为是间皮瘤阴性标志物的抗体中，最佳鉴别标志物是CEA、MOC-31、Ber-EP4、BG-8和B72.3。建议根据可获得性以及在特定实验室中哪些标志物能产生良好染色结果来选择一组四个标志物（两个阳性和两个阴性）。由于它们对间皮瘤的特异性和敏感性，最佳组合似乎是钙视网膜蛋白和细胞角蛋白5/6（或WT1）作为阳性标志物，CEA和MOC-31（或B72.3、Ber-EP4或BG-8）作为阴性标志物。还提供了对文献的广泛而详细的综述。
