Loss of expression of BAP1 is very rare in non-small cell lung carcinoma

Our plain-English summary of Loss of expression of BAP1 is very rare in non-small cell lung carcinoma, by J. Andrici, T.R. Parkhill, J. Jung, et al (Pathology, 2016).

The study

• Authors: J. Andrici, T.R. Parkhill, J. Jung, K.L. Wardell, B. Verdonk, A. Singh, L. Sioson, A. Clarkson, N. Watson, A. Sheen, M. Farzin, C.W. Toon, A.J. Gill
• Journal: Pathology
• Published: 2016;48(4):336-40
• Cited by: 34 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Germline mutations of the BAP1 gene have been implicated in a cancer predisposition syndrome which includes mesothelioma, uveal melanoma, cutaneous melanocytic lesions, renal cell carcinoma, and possibly other malignancies. Double hit inactivation of BAP1 with subsequent loss of expression of the BAP1 protein also occurs in approximately 50% of mesotheliomas. The link between BAP1 mutation and lung cancer is yet to be fully explored. We sought to assess BAP1 expression in a large cohort of lung cancers undergoing surgery with curative intent. We searched the Anatomical Pathology database of our institution for lung cancer patients undergoing surgery with curative intent between 2000 and 2010. Immunohistochemistry for BAP1 was then performed in tissue microarray format. Our cohort included 257 lung cancer patients, of which 155 (60%) were adenocarcinomas and 72 (28%) were squamous cell carcinomas, with no other subtype comprising more than 3%. BAP1 loss of expression was found in only one lung cancer. We conclude that BAP1 mutation occurs very infrequently (0.4%) in non-small cell lung cancer. Given that the pathological differential diagnosis between lung carcinoma and mesothelioma may sometimes be difficult, this finding increases the specificity of loss of expression for BAP1 for the diagnosis of mesothelioma.

Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.

In plain English

This study, from Royal North Shore Hospital in Sydney, Australia, examined how often lung cancers lose the BAP1 protein. The authors note that this loss occurs in about half of mesotheliomas. They searched their pathology database for lung cancers removed by surgery with curative intent between 2000 and 2010 and stained tumour samples for BAP1. Of 270 patients found, 257 had enough tissue to test. Of these, 155 had adenocarcinoma and 72 had squamous cell carcinoma. All but one tumour stained positive for BAP1. The single negative case, 0.4% of the cohort, was a 35 mm adenocarcinoma in a 58-year-old woman. Further staining confirmed it was lung adenocarcinoma and not a misdiagnosed mesothelioma. The study measured protein staining, not genes, and did not look at asbestos exposure. The authors concluded that BAP1 staining can be added to the tests pathologists use to tell lung carcinoma from mesothelioma. They noted that their finding does not completely rule out lung cancer being part of the inherited BAP1 cancer syndrome.

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 pathology study of archived surgical lung cancer specimens, using immunohistochemistry (protein staining) for BAP1 on a tissue microarray
• Who was studied: 257 patients whose lung cancers were surgically removed with curative intent at Royal North Shore Hospital, Sydney, Australia, diagnosed 2000 to 2010. 270 patients were identified and 13 were excluded for lack of usable tissue. The 257 included 155 adenocarcinomas (60%) and 72 squamous cell carcinomas (28%).
• Exposure: No asbestos or other exposure was studied. The study measured whether tumour cells showed BAP1 protein staining.
• Main results:
  • All but one of the 257 lung cancers showed diffusely positive BAP1 staining.
  • Loss of BAP1 expression was found in one case, 0.4% of the 257 patients.
  • The BAP1-negative case was a 35 mm adenocarcinoma in the right middle lobe of a 58-year-old female.
  • Additional staining confirmed the negative case was lung adenocarcinoma, not a misdiagnosed epithelioid mesothelioma.
• The authors' conclusion: The authors concluded that loss of BAP1 expression is very rare (0.4%) in primary non-small cell lung carcinoma. In their view, BAP1 staining can be added to the diagnostic panel used to distinguish lung carcinoma from mesothelioma.
• Limitations the authors state:
  • The authors stated that their finding does not completely exclude lung carcinoma being part of the hereditary cancer syndrome linked to BAP1 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, Carcinoma, Germline Mutation, Mesothelioma, Lung Cancer, Pathology, Immunohistochemistry, Adenocarcinoma.

Related studies

• 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)
• Loss of BRCA1-associated protein 1 (BAP1) expression is rare in non-small cell lung cancer — D. Owen, B.S. Sheffield, et al. (2017)
• Loss of expression of BAP1 is a useful adjunct, which strongly supports the diagnosis of mesothelioma in effusion cytology — J. Andrici, A. Sheen, et al. (2015)
• Loss of expression of BAP1 predicts longer survival in mesothelioma — M. Farzin, C.W. Toon, et al. (2015)
• Germline BAP1 mutations predispose also to multiple basal cell carcinomas — A. de la Fouchardière, O. Cabaret, et al. (2015)
• A recurrent germline BAP1 mutation and extension of the BAP1 tumor predisposition spectrum to include basal cell carcinoma — K.A. Wadt, L.G. Aoude, et al. (2015)

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