Chaouche-Mazouni Siham, Scherpereel Arnaud, Zaamoum Rima, Mihalache Adriana, Amir Zine-Charaf, Lebaïli Nemcha, Delaire Baptiste, Gosset Pierre
Department of Biology, Kouba High School, Algiers, Algeria.
Department of Pulmonary and Thoracic Oncology, Lille University Hospital, Lille, France.
Ann Diagn Pathol. 2015 Aug;19(4):193-7. doi: 10.1016/j.anndiagpath.2015.03.007. Epub 2015 Apr 14.
Epithelioid malignant pleural mesothelioma (MPM) can easily be confused with lung adenocarcinomas (ACAs). In serous effusion, claudin (cldn) 3 is shown to be useful in the diagnosis of mesothelioma vs ACAs. Cldn15 is reported to be overexpressed in epithelioid mesothelioma and absent in human airway epithelium. The aim was to assess the value of cldn3 and cldn4 compared to that of BerEp4 and thyroid transcription factor-1 (TTF1) in differentiating lung ACA from epithelioid MPM and to examine the expression of cldn15 in these tumors. The expression of cldn3, cldn4, cldn15, BerEp4, and TTF1 was examined by immunohistochemistry in a total of 62 human specimen including 28 epithelioid MPMs and 34 ACAs of the lung. In lung ACA, cldn4 was strongly expressed in all 34 (100%) specimens followed by cldn3 in 33 (97%) of 34. BerEp4 was expressed in 32 (94.1%) of 34. TTF1 reacted for only 20 (58.82%) of 34 cases of lung ACA. In MPM specimens, the expression of cldn3 and4 as well as that of TTF1 was completely absent. In contrast, BerEp4 was focally expressed in 5 (17.85%) of 28 cases of epithelioid MPM. Cldn15 was strongly expressed in 53% pf epithelioid MPMs but also in 50% of lung ACAs. Its expression was moderate in normal pleura and limited in normal lung. Cldn3 and cldn4 appear to be the best performing carcinoma markers in discriminating lung ACA from mesothelioma compared with BerEp4 and TTF1. There is no differential expression of cldn15 between the 2 pathologies. However, the limited cldn15 expression in normal tissues and high expression in tumors make it an attractive candidate for cancer therapy.
上皮样恶性胸膜间皮瘤(MPM)很容易与肺腺癌(ACA)混淆。在浆液性胸腔积液中,紧密连接蛋白(cldn)3被证明在间皮瘤与ACA的诊断中有用。据报道,cldn15在上皮样间皮瘤中过表达,而在人类气道上皮中不存在。目的是评估与BerEp4和甲状腺转录因子-1(TTF1)相比,cldn3和cldn4在区分肺ACA与上皮样MPM中的价值,并检测这些肿瘤中cldn15的表达。通过免疫组织化学检测了总共62例人类标本中cldn3、cldn4、cldn15、BerEp4和TTF1的表达,其中包括28例上皮样MPM和34例肺ACA。在肺ACA中,34例标本中有34例(100%)cldn4强烈表达,34例中有33例(97%)cldn3表达。34例中有32例(94.1%)表达BerEp4。34例肺ACA病例中只有20例(58.82%)TTF1呈阳性反应。在MPM标本中,cldn3和4以及TTF1均完全不表达。相反,28例上皮样MPM中有5例(17.85%)BerEp4呈局灶性表达。53%的上皮样MPM中cldn15强烈表达,但50%的肺ACA中也有表达。其在正常胸膜中表达中等,在正常肺中表达有限。与BerEp4和TTF1相比,cldn3和cldn4似乎是区分肺ACA与间皮瘤的最佳癌标志物。两种病理类型之间cldn15没有差异表达。然而,cldn15在正常组织中表达有限而在肿瘤中高表达,这使其成为癌症治疗的一个有吸引力的候选靶点。