摘要目的 探讨BRCA相关蛋白1(BRCA associated protein 1,BAP1)在恶性间皮瘤、肺腺癌、肺鳞癌和癌肉瘤中表达情况及其在鉴别诊断中的作用.方法 选取恶性间皮瘤22例,其中上皮样型17例,肉瘤样型2例,双相型3例.另选取侵犯胸膜的非小细胞肺癌共80例(肺腺癌40例、肺鳞癌40例)和全身各部位癌肉瘤15例作为对照.应用免疫组织化学方法检测BAP1在各组病例的表达情况,并分析各组表达差异.同时所有病例均检测了常规用于间皮瘤鉴别诊断的抗体组合,包括calretinin、WT1、细胞角蛋白5/6、D2-40、CAM5.2、癌胚抗原、甲状腺转录因子1、Napsin A、p63和p40.结果 所有80例非小细胞肺癌和15例癌肉瘤均BAP1核表达阳性,而64%(14/22)恶性间皮瘤出现BAP1表达缺失,两者差异有统计学意义(P<0.01).间皮瘤诊断标志物组合中,增加BAP1后,诊断恶性间皮瘤的诊断正确度达93%.BAP1灶性表达表明肿瘤细胞具有多克隆性.结论 BAP1核表达缺失有助于鉴别恶性间皮瘤和非小细胞肺癌.因此推荐BAP1与其他间皮瘤抗体一起应用于恶性间皮瘤的诊断,提高恶性间皮瘤的诊断准确性.

abstractsObjective To investigate the expression of BRCA-associated protein 1 ( BAP1) in malignant mesothelioma, non-small cell lung cancer and carcinosarcoma, and its application in the differential diagnosis. Methods Twenty-two cases of malignant mesothelioma including 17 epithelioid type, 2 sarcomatoid type and 3 biphasic type were collected. As the study control, 80 non-small cell lung cancers infringement pleural membrane( including 40 lung adenocarcinomas and 40 lung squamous cell carcinomas) and 15 carcinosarcomas were included. BAP1 expression was detected using immunohistochemical method. A differential diagnosis antibody panel, including calretinin, WT1, CK5/6, D2-40, CAM5. 2,CEA, TTF1, Napsin A, p63 and p40 was tested in all cases. Results All 80 cases of non-small cell lung cancer and 15 cases of carcinosarcoma were BAP1 positive. In contrast,64% (14/22) of malignant mesotheliomas lost BAP1 expression (P<0. 01). Addition of BAP1 to the mesothelioma marker panel, the diagnostic accuracy of malignant mesothelioma was enhanced to 93%. Focal expression of BAP1 in tumors suggested multiclonal evolution of mesothelioma. Conclusions Loss of BAP1 expression helps to confirm the diagnosis of malignant mesothelioma whereas all non-small cell lung cancer expresses BAP1. It is therefore recommended that BAP1 can be used in conjunction with other immunohistochemical markers to improve the diagnostic accuracy of malignant mesothelioma.