Positive nuclear BAP1 immunostaining helps differentiate non-small cell lung carcinomas from malignant mesothelioma

Our plain-English summary of Positive nuclear BAP1 immunostaining helps differentiate non-small cell lung carcinomas from malignant mesothelioma, by M. Carbone, D. Shimizu, A. Napolitano, et al (Oncotarget, 2016).

The study

• Authors: M. Carbone, D. Shimizu, A. Napolitano, M. Tanji, H.I. Pass, H. Yang, S. Pastorino
• Journal: Oncotarget
• Published: 2016;7(37):59314-59321
• Cited by: 51 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

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.

In plain English

This pathology study tested whether staining tumor tissue for the protein BAP1 helps tell malignant mesothelioma apart from non-small cell lung cancer. The authors stained 45 lung cancer samples (32 adenocarcinomas and 13 squamous cell carcinomas) and 10 mesothelioma biopsies diagnosed at the Queens Medical Center in Honolulu, plus 25 mesothelioma biopsies from New York University, for 35 mesotheliomas in all. The study did not examine asbestos exposure. All 45 lung cancers showed nuclear BAP1 staining, although in 2 adenocarcinomas some tumor nodules were BAP1 negative. Of the 35 mesotheliomas, 22 (63%) had entirely lost BAP1 staining. Lack of nuclear BAP1 staining was associated with mesothelioma (Fisher's exact test, P = 5.4 times 10 to the power of minus 11). Other standard stains, tested on the lung cancers and 10 of the mesotheliomas, gave results the authors described as in agreement with earlier studies. The authors noted that patchy BAP1 loss could cause sampling errors in very small biopsies. They concluded that BAP1 should be included in the stain panel used to distinguish lung cancer from mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Diagnostic pathology (immunohistochemistry) study comparing tumor biopsies
• Who was studied: 45 non-small cell lung cancers (32 primary lung adenocarcinomas, 13 primary lung squamous cell carcinomas) and 10 malignant mesothelioma biopsies from Queens Medical Center, Honolulu, Hawaii, plus 25 malignant mesothelioma biopsies from New York University. This gave 35 mesotheliomas: 20 epithelial, 8 biphasic, 7 sarcomatoid.
• Exposure: No asbestos or other exposure was studied. The study examined staining of tumor tissue for BAP1 protein and for a panel of other diagnostic markers.
• Main results:
  • All 45 non-small cell lung cancer samples stained positive for nuclear BAP1
  • In 2 of the lung adenocarcinomas, BAP1 staining was patchy: some tumor areas stained and some tumor nodules were BAP1 negative
  • BAP1 staining was entirely lost in 22 of 35 (63%) malignant mesothelioma samples
  • Focal (partial) BAP1 staining was seen in 6 of 20 (30%) epithelial mesotheliomas and 3 of 8 (37%) biphasic mesotheliomas
  • Lack of nuclear BAP1 staining was associated with mesothelioma (two-tailed Fisher's exact test, P = 5.4 times 10 to the power of minus 11)
  • In the 10 mesotheliomas tested with the standard panel, tumor cells were mostly positive for WT1, calretinin, D2-40, CK5 and CAM5.2 and negative for TTF-1, p63 and Napsin-A
  • Among the lung squamous cell carcinomas, calretinin was focally positive in 23% and D2-40 in 77%
• The authors' conclusion: The authors concluded that their findings justify including BAP1 in the panel of stains used to tell lung cancer from mesothelioma
• Limitations the authors state:
  • Because some tumors contained areas that had lost BAP1, the authors noted a risk of sampling error if only very small needle biopsies or tumor arrays were examined

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: BAP1, Carcinoma, Mesothelioma, Differential Diagnosis, Lung Cancer, Non-Small Cell Lung Cancer, Adenocarcinoma, Squamous Cell Carcinoma.

Related studies

• Loss of BRCA1-associated protein 1 (BAP1) expression is rare in non-small cell lung cancer — D. Owen, B.S. Sheffield, et al. (2017)
• Nuclear Brachyury Expression Is Consistent in Chordoma, Common in Germ Cell Tumors and Small Cell Carcinomas, and Rare in Other Carcinomas and Sarcomas: An Immunohistochemical Study of 5229 Cases — M. Miettinen, Z. Wang, et al. (2015)
• Loss of BAP1 Expression in Atypical Mesothelial Proliferations Helps to Predict Malignant Mesothelioma — R. Pillappa, J.J. Maleszewski, et al. (2018)
• Diagnostic application of BAP1 immunohistochemistry to differentiate pleural mesothelioma from metastatic pleural tumours — M. Yoshimura, Y. Kinoshita, et al. (2017)
• BAP1 regulates IP3R3-mediated Ca2+ flux to mitochondria suppressing cell transformation — A. Bononi, C. Giorgi, et al. (2017)
• Utility of BRCA1-associated protein 1 immunoperoxidase stain to differentiate benign versus malignant mesothelial proliferations in cytologic specimens — Z. McCroskey, G. Staerkel, et al. (2017)

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