BAP1 facilitates diagnostic objectivity, classification, and prognostication in malignant pleural mesothelioma

Our plain-English summary of BAP1 facilitates diagnostic objectivity, classification, and prognostication in malignant pleural mesothelioma, by S.M. McGregor, R. Dunning, E. Hyjek, et al (Human Pathology, 2015).

The study

• Authors: S.M. McGregor, R. Dunning, E. Hyjek, W. Vigneswaran, A.N. Husain, T. Krausz
• Journal: Human Pathology
• Published: 2015;46(11):1670-8
• Cited by: 94 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

BRCA-associated protein 1 (BAP1) has emerged as a promising biomarker for malignant pleural mesothelioma (MPM). Loss of BAP1 expression can occur by a variety of mechanisms, but reports on incidence are variable and the clinical significance is unclear. In order to investigate the diagnostic and prognostic significance of BAP1, we constructed a tissue microarray consisting of 111 MPM cases and performed BAP1 immunohistochemistry. BAP1 was lost in 77% of epithelioid cases (n=58) but was retained in all sarcomatoid cases (n=10); 49% of biphasic cases showed loss (n=43), and BAP1-negative cases demonstrated loss of staining in both the epithelioid and sarcomatoid components. All non-neoplastic mesothelial tissues (n=20) retained BAP1, resulting in a sensitivity, specificity, positive predictive value, and negative predictive value of 61%, 100%, 100%, and 32%, respectively. Moreover, BAP1 expression in spindled mesothelium enabled discrimination of reactive and malignant cells, thus providing a more objective means of distinguishing epithelioid from biphasic morphology compared to histology alone. Nonetheless, BAP1 staining was patchy in some benign mesothelial neoplasms, which raises concern for using BAP1 in small biopsies. Kaplan-Meier analysis demonstrated a significant improvement in overall survival with BAP1 loss, but this did not reach significance in multivariate analysis accounting for histologic subtype. When only epithelioid cases were analyzed there was a trend toward increased survival, but it did not reach significance. We conclude that BAP1 loss is frequent in epithelioid MPM, which is in turn associated with improved survival, and that it can have additional clinical significance by facilitating histologic classification.

Copyright © 2015 Elsevier Inc. All rights reserved.

In plain English

This laboratory study looked at stored tumor tissue from 111 people with malignant pleural mesothelioma (89 men and 22 women, average age 69) found in University of Chicago pathology archives for 2004 to 2013. The authors stained the samples for BAP1, a protein. The study did not look at asbestos exposure. BAP1 was lost in 61% of tumors overall: 77% of epithelioid, 49% of biphasic, and none of the sarcomatoid tumors. All 20 non-cancerous (reactive) mesothelial lesions kept BAP1. Comparing the 111 mesothelioma cases with these 20 lesions, BAP1 loss as a test showed sensitivity 61%, specificity 100%, positive predictive value 100% and negative predictive value 32%. Staining was patchy and weak in some benign mesothelial tumors, so the authors urged caution with small biopsies. BAP1 loss was linked to better survival when looked at alone, but not once tumor subtype was taken into account. In epithelioid cases alone, a trend toward better survival did not reach significance. The authors concluded that BAP1 helps diagnose and classify mesothelioma, and so indirectly gives prognostic information.

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: archived tumor samples were placed on a tissue microarray, stained for the protein BAP1 (immunohistochemistry), and compared with chart-reviewed survival
• Who was studied: 111 cases of malignant pleural mesothelioma (58 epithelioid, 43 biphasic, 10 sarcomatoid) from University of Chicago pathology archives, 2004 to 2013. The patients were 89 men and 22 women with an average age of 69. Controls were benign and reactive mesothelial tissues.
• Exposure: No asbestos or other environmental or occupational exposure was studied. The factor examined was whether tumor cells showed BAP1 protein in their nuclei on staining.
• Main results:
  • BAP1 staining was lost in 61% of all mesothelioma cases
  • BAP1 was lost in 77% of epithelioid, 49% of biphasic and 0% of sarcomatoid cases
  • All 20 reactive (non-cancerous) mesothelial lesions kept BAP1 staining
  • As a single test, loss of BAP1 had a sensitivity of 61%, specificity of 100%, positive predictive value of 100% and negative predictive value of 32%. These figures came from comparing the mesothelioma cases with the 20 non-neoplastic mesothelial tissues, which all kept BAP1.
  • BAP1 staining was patchy and weak in some benign multicystic and well-differentiated papillary mesotheliomas
  • In BAP1-negative biphasic cases, both the epithelioid and sarcomatoid parts lacked BAP1
  • Spindle-shaped cells mixed among malignant epithelioid islands often kept BAP1. The authors interpreted these as reactive cells, which helped them tell epithelioid tumors with scarring apart from biphasic tumors.
  • No significant differences in clinical characteristics were found between BAP1-positive and BAP1-negative cases
  • In analysis of BAP1 alone (univariate), BAP1 loss was associated with better overall survival
  • When histologic subtype was included in the analysis, subtype remained an independent predictor of survival but BAP1 did not
  • Among epithelioid cases only, there was a trend toward better survival with BAP1 loss that did not reach statistical significance. Among biphasic cases only, no effect was seen.
• The authors' conclusion: The authors concluded that BAP1 staining helps both to diagnose malignant pleural mesothelioma and to classify its histologic subtype, and in that way indirectly provides prognostic information
• Limitations the authors state:
  • Only a small number of sarcomatoid cases were examined
  • Because of patchy staining in some benign tumors, BAP1 results on small biopsies or cytology samples could be misleading
  • A single institution could not gather enough cases to detect subtle survival differences

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, Pleural Mesothelioma, Biomarker, Immunohistochemistry, Epithelioid, Sarcomatoid, Biphasic Mesothelioma, Mesothelium.

Related studies

• BAP1 immunohistochemistry has limited prognostic utility as a complement of CDKN2A (p16) fluorescence in situ hybridization in malignant pleural mesothelioma — S.M. McGregor, J. McElherne, et al. (2017)
• BAP1 (BRCA1-associated protein 1) is a highly specific marker for differentiating mesothelioma from reactive mesothelial proliferations — M. Cigognetti, S. Lonardi, et al. (2015)
• 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)
• The diagnostic role of BAP1 in serous effusions — B. Davidson, M. Tötsch, et al. (2018)
• Diagnostic application of BAP1 immunohistochemistry to differentiate pleural mesothelioma from metastatic pleural tumours — M. Yoshimura, Y. Kinoshita, et al. (2017)
• Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma — A. Shinozaki-Ushiku, T. Ushiku, et al. (2017)

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