Department of Pathology, Hyogo College of Medicine, Hyogo, Japan.
Mod Pathol. 2010 Nov;23(11):1458-66. doi: 10.1038/modpathol.2010.134. Epub 2010 Jul 23.
Malignant pleural mesothelioma is a refractory tumor with poor prognosis associated with asbestos exposure. Pleural effusion is frequently observed in patients with malignant pleural mesothelioma, and cytological analysis is effective to detect malignant pleural mesothelioma. However, cytological discrimination between malignant pleural mesothelioma and reactive mesothelium is often difficult. Increased expression of CD146, a cell adhesion molecule, has been reported to be closely associated with an advanced stage of malignant melanoma, prostate cancer, and ovarian cancer. In this study, to evaluate the diagnostic utility of CD146 for discrimination between malignant pleural mesothelioma and reactive mesothelium, we examined immunocytochemical expression of CD146 in malignant pleural mesothelioma and reactive mesothelium using two clones of CD146 antibody, OJ79 and EPR3208, on smear specimens of effusion fluids. Immunocytochemical stains were semiquantitatively scored on the basis of immunostaining intensity (0, negative; 1, weak positive; 2, moderate positive; and 3, strong positive). CD146 expression was detected in 15 of 16 malignant pleural mesothelioma with median immunostaining score of 3 by OJ79, and in 19 of 21 malignant pleural mesothelioma with median immunostaining score of 2 by EPR3208. Strong immunoreactivity of CD146 was observed at the apposing surfaces of cell-cell interactions on the plasma membrane of mesothelioma cells. In addition, one OJ79-negative case of malignant pleural mesothelioma was positive for CD146 by EPR3208 and two EPR3208-negative cases of malignant pleural mesothelioma were CD146 positive by OJ79, showing that all 23 malignant pleural mesothelioma cases were positive for CD146 by either OJ79 or EPR3208. On the other hand, CD146 expression was undetectable in all reactive mesothelium cases by OJ79 and EPR3208. The sensitivity of OJ79 and EPR3208 was 94 and 90%, respectively, and the specificity was 100% for both clones. We propose that CD146 is a sensitive and specific immunocytochemical marker enabling differential diagnosis of malignant pleural mesothelioma from reactive mesothelium.
恶性胸膜间皮瘤是一种预后不良的难治性肿瘤,与石棉暴露有关。恶性胸膜间皮瘤患者常出现胸腔积液,细胞学分析有助于检测恶性胸膜间皮瘤。然而,恶性胸膜间皮瘤与反应性间皮之间的细胞学鉴别通常较为困难。已有报道称,细胞黏附分子 CD146 的表达增加与恶性黑色素瘤、前列腺癌和卵巢癌的晚期密切相关。在这项研究中,为了评估 CD146 用于鉴别恶性胸膜间皮瘤和反应性间皮的诊断效用,我们使用两种 CD146 抗体 OJ79 和 EPR3208 ,在胸腔积液涂片标本上检测 CD146 在恶性胸膜间皮瘤和反应性间皮中的免疫细胞化学表达。免疫细胞化学染色根据免疫染色强度(0,阴性;1,弱阳性;2,中度阳性;3,强阳性)进行半定量评分。OJ79 检测到 16 例恶性胸膜间皮瘤中的 15 例,免疫染色评分中位数为 3,EPR3208 检测到 21 例恶性胸膜间皮瘤中的 19 例,免疫染色评分中位数为 2。在间皮瘤细胞膜的细胞-细胞相互作用的毗邻表面观察到 CD146 的强免疫反应性。此外,1 例 OJ79 阴性的恶性胸膜间皮瘤病例对 EPR3208 呈 CD146 阳性,2 例 EPR3208 阴性的恶性胸膜间皮瘤病例对 OJ79 呈 CD146 阳性,表明 23 例恶性胸膜间皮瘤病例均对 OJ79 或 EPR3208 呈 CD146 阳性。另一方面,OJ79 和 EPR3208 均未检测到所有反应性间皮的 CD146 表达。OJ79 和 EPR3208 的敏感性分别为 94%和 90%,两种克隆的特异性均为 100%。我们提出 CD146 是一种敏感且特异的免疫细胞化学标志物,可用于恶性胸膜间皮瘤与反应性间皮的鉴别诊断。