Carbone Michele, Shimizu David, Napolitano Andrea, Tanji Mika, Pass Harvey I, Yang Haining, Pastorino Sandra
Thoracic Oncology Program, University of Hawaii Cancer Center, Honolulu, HI, USA.
Department of Pathology, Queen Medical Center, Honolulu, HI, USA.
Oncotarget. 2016 Sep 13;7(37):59314-59321. doi: 10.18632/oncotarget.10653.
The differential diagnosis between pleural malignant mesothelioma (MM) and lung cancer is often challenging. Immunohistochemical (IHC) stains used to distinguish these malignancies include markers that are most often positive in MM and less frequently positive in carcinomas, and vice versa. However, in about 10-20% of the cases, the IHC results can be confusing and inconclusive, and novel markers are sought to increase the diagnostic accuracy.We stained 45 non-small cell lung cancer samples (32 adenocarcinomas and 13 squamous cell carcinomas) with a monoclonal antibody for BRCA1-associated protein 1 (BAP1) and also with an IHC panel we routinely use to help differentiate MM from carcinomas, which include, calretinin, Wilms Tumor 1, cytokeratin 5, podoplanin D2-40, pankeratin CAM5.2, thyroid transcription factor 1, Napsin-A, and p63. Nuclear BAP1 expression was also analyzed in 35 MM biopsies. All 45 non-small cell lung cancer biopsies stained positive for nuclear BAP1, whereas 22/35 (63%) MM biopsies lacked nuclear BAP1 staining, consistent with previous data. Lack of BAP1 nuclear staining was associated with MM (two-tailed Fisher's Exact Test, P = 5.4 x 10-11). Focal BAP1 staining was observed in a subset of samples, suggesting polyclonality. Diagnostic accuracy of other classical IHC markers was in agreement with previous studies. Our study indicated that absence of nuclear BAP1 stain helps differentiate MM from lung carcinomas. We suggest that BAP1 staining should be added to the IHC panel that is currently used to distinguish these malignancies.
胸膜恶性间皮瘤（MM）与肺癌的鉴别诊断往往具有挑战性。用于区分这些恶性肿瘤的免疫组织化学（IHC）染色包括在MM中最常呈阳性而在癌中较少呈阳性的标志物，反之亦然。然而，在约10 - 20%的病例中，IHC结果可能令人困惑且无定论，因此需要寻找新的标志物以提高诊断准确性。我们用一种针对BRCA1相关蛋白1（BAP1）的单克隆抗体对45个非小细胞肺癌样本（32个腺癌和13个鳞状细胞癌）进行染色，同时还用我们常规用于帮助区分MM与癌的一组IHC标志物进行染色，这些标志物包括钙视网膜蛋白、威尔姆斯瘤1、细胞角蛋白5、足板蛋白D2 - 40、泛角蛋白CAM5.2、甲状腺转录因子1、Napsin - A和p63。还对35个MM活检样本中的核BAP1表达进行了分析。所有45个非小细胞肺癌活检样本的核BAP1染色均呈阳性，而35个MM活检样本中有22个（63%）缺乏核BAP1染色，这与先前的数据一致。缺乏BAP1核染色与MM相关（双尾Fisher精确检验，P = 5.4×10 - 11）。在一部分样本中观察到局灶性BAP1染色，提示多克隆性。其他经典IHC标志物的诊断准确性与先前的研究一致。我们的研究表明，缺乏核BAP1染色有助于将MM与肺癌区分开来。我们建议应将BAP1染色添加到目前用于区分这些恶性肿瘤的IHC标志物组中。
