Loss of BRCA1-associated protein 1 (BAP1) expression is rare in non-small cell lung cancer

Our plain-English summary of Loss of BRCA1-associated protein 1 (BAP1) expression is rare in non-small cell lung cancer, by D. Owen, B.S. Sheffield, D. Ionescu, et al (Human Pathology, 2017).

The study

• Authors: D. Owen, B.S. Sheffield, D. Ionescu, A. Churg
• Journal: Human Pathology
• Published: 2017;60:82-85
• Cited by: 23 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene involved in regulation of the cell cycle, cellular differentiation, repair of DNA damage, and apoptosis. In the distinction of malignant mesothelioma from benign mesothelial proliferations, immunohistochemical loss of BAP1, the protein expressed by the BAP1 gene, has proven highly specific for malignant mesothelioma. However, few studies have investigated the rate of BAP1 loss in tumors that commonly metastasize to the pleura. Our objective is to determine the rate of BAP1 loss in non-small cell lung cancer (NSCLC). Immunohistochemistry for BAP1 was performed using tissue microarrays containing 133 confirmed cases of NSCLC (80 of lung adenocarcinoma and 53 of squamous cell carcinoma). Cases were interpreted as showing BAP1 loss if nuclear staining was completely absent in all tumor cells and present in stromal and inflammatory cells that served as internal controls. Cases showing no BAP1 staining in the internal controls were excluded. After exclusion of 32 cases for technical reasons, only 1 case of pulmonary adenocarcinoma of 101 cases of NSCLC (69 adenocarcinoma and 32 squamous cell carcinoma; 1.0% of cases) showed BAP1 loss. We conclude that loss of BAP1 expression is a rare event in NSCLC. Therefore, BAP1 is a potentially useful addition to the immunohistochemical markers used to distinguish mesothelioma from pleural metastasis of NSCLC.

Copyright © 2016 Elsevier Inc. All rights reserved.

In plain English

This laboratory study, by Vancouver pathologists, asked how often non-small cell lung cancer (NSCLC) loses a protein called BAP1. Loss of BAP1 on tissue staining helps pathologists diagnose malignant mesothelioma, so the authors wanted to know how often NSCLC, which can spread to the pleura (the lining around the lung), also loses it. They stained archived, surgically removed lung tumors from 133 cases: 80 lung adenocarcinomas and 53 squamous cell carcinomas. Thirty-two were excluded for technical reasons, leaving 101 (69 adenocarcinomas, 32 squamous cell carcinomas). Only one tumor, an adenocarcinoma, showed BAP1 loss: 1.4% of adenocarcinomas and 1.0% of all the NSCLCs. Every squamous cell carcinoma kept BAP1. That patient was a woman with no smoking history, and she was not tested for an inherited BAP1 mutation. Citing their own results and another study's, the authors suggested that, when deciding between mesothelioma and metastatic NSCLC, BAP1 loss would effectively rule out NSCLC. They noted that the stain's sensitivity for mesothelioma is limited. The study did not look at asbestos exposure and did not test mesothelioma tissue.

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: Retrospective laboratory study: immunohistochemical staining for BAP1 on tissue microarrays made from archived lung cancer specimens
• Who was studied: 133 surgically resected lung cancers (80 adenocarcinomas, 53 squamous cell carcinomas) from the British Columbia Cancer Agency and Vancouver General Hospital, Canada. These were primary lung tumors, not cases selected for pleural spread. 101 were analysable after exclusions. Dates were not given.
• Exposure: Not an exposure study: no asbestos or fiber exposure was assessed. What was studied was BAP1 protein staining (immunohistochemistry) of tumor tissue
• Main results:
  • Of 133 cases, 32 were excluded for faint or absent staining in internal controls or loss of the tissue core, leaving 101 (69 adenocarcinomas and 32 squamous cell carcinomas)
  • One lung adenocarcinoma showed BAP1 loss: 1.4% of the lung adenocarcinomas and 1.0% of the 101 NSCLCs
  • The other 100 NSCLCs, including all squamous cell carcinomas, retained BAP1
  • The single adenocarcinoma with BAP1 loss came from a woman with no smoking history and no personal or family history of other BAP1-associated cancer
• The authors' conclusion: The authors concluded that BAP1 loss is very rare in NSCLC. Based on their results and those of Andrici et al, they suggested that, when the diagnosis is mesothelioma versus metastatic NSCLC, BAP1 loss would effectively rule out NSCLC.
• Limitations the authors state:
  • The authors note that BAP1 staining of mesotheliomas is limited by sensitivity
  • The one patient with BAP1 loss was not tested for an inherited (germline) mutation

Topics

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

Medical terms in this study, explained in our Lexicon: BAP1, Non-Small Cell Lung Cancer, Tumor Suppressor Gene, Apoptosis, Malignant Mesothelioma, Metastasis, Pleura, Immunohistochemistry.

Related studies

• Loss of expression of BAP1 is very rare in non-small cell lung carcinoma — J. Andrici, T.R. Parkhill, et al. (2016)
• Loss of BRCA1-associated protein 1 (BAP1) expression is useful in diagnostic cytopathology of malignant mesothelioma in effusions — I. Cozzi, F.A. Oprescu, et al. (2018)
• Loss of BAP1 expression is very rare in peritoneal and gynecologic serous adenocarcinomas and can be useful in the differential diagnosis with abdominal mesothelioma — J. Andrici, J. Jung, et al. (2016)
• BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations — M. Cigognetti, S. Lonardi, et al. (2015)
• The value of BRCA-1-associated protein 1 expression and cyclin-dependent kinase inhibitor 2A deletion to distinguish peritoneal malignant mesothelioma from peritoneal location of carcinoma in effusion cytology specimens — W. Althakfi, S. Gazzo, et al. (2020)
• Loss of expression of BAP1 predicts longer survival in mesothelioma — M. Farzin, C.W. Toon, et al. (2015)

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