Diagnostic Utility of BAP1, EZH2 and Survivin in Differentiating Pleural Epithelioid Mesothelioma and Reactive Mesothelial Hyperplasia: Immunohistochemical Study

Our plain-English summary of Diagnostic Utility of BAP1, EZH2 and Survivin in Differentiating Pleural Epithelioid Mesothelioma and Reactive Mesothelial Hyperplasia: Immunohistochemical Study, by S.A. Hakim, H.H. Abou Gabal (Pathology Oncology Research, 2021).

The study

• Authors: S.A. Hakim, H.H. Abou Gabal
• Journal: Pathology Oncology Research
• Published: 2021;27:600073
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Epithelioid mesothelioma (EM) is the commonest subtype of malignant pleural mesothelioma. Its histopathological discrimination from reactive mesothelial hyperplasia (RMH) could be challenging. Thus, an immunohistochemical panel is mandatory for better discrimination. BAP1 is a newly identified diagnostic marker whose loss is specific to malignant mesothelioma. EZH2 overexpression is reported in different cancers, but its relation to BAP1 in malignant mesothelioma has not been fully understood. Survivin expression is said to be significantly higher in EM than in non-neoplastic pleural tissue, but its diagnostic utility as an immunohistochemical marker has not been thoroughly investigated in this field. To the best of our knowledge, no previous studies have been conducted to assess the diagnostic accuracy of the combined use of these three nuclear markers (BAP1, EZH2 and Survivin) in discriminating pleural EM from RMH. Methods: This retrospective study includes two groups: 81 cases of pleural EM and 67 cases of RMH, retrieved from the archives of Pathology Department of Ain Shams University Hospitals and Ain-Shams University Specialized Hospital during the period from January 2016 to December 2019. An immunohistochemical study was performed using BAP1, EZH2 and Survivin antibodies. Results: There were highly statistically significant relations between study groups as regards the studied markers (p = 0.001 for each). The specificity was 100% for all combinations of immunohistochemical markers. Sensitivity of any combination of the immunohistochemical markers used in this study was found to be higher than the sensitivity of any of these markers used individually. The combination of all three markers showed the highest diagnostic accuracy (95.9%) and the highest sensitivity (92.6%). However, the combination of Survivin and EZH2 yielded the same diagnostic accuracy and sensitivity. Conclusion: Adding EZH2, Survivin and BAP1 to the diagnostic IHC panel for differentiating pleural EM and RMH could enhance diagnostic sensitivity. Moreover, Survivin is a potentially promising marker in this context, especially when combined with EZH2.

Copyright © 2021 Hakim and Abou Gabal.

In plain English

This laboratory study, by two pathologists at Ain Shams University in Cairo, Egypt, tested whether three tissue stains (BAP1, EZH2 and Survivin) help tell pleural epithelioid mesothelioma, a cancer of the lining around the lungs, apart from reactive mesothelial hyperplasia, a non-cancerous overgrowth of the same lining cells. The authors re-examined archived biopsies from 81 mesothelioma cases and 67 hyperplasia cases diagnosed from January 2016 to December 2019. Among the mesothelioma cases, 60.5% showed loss of BAP1, 44.4% showed high EZH2 and 67.9% were Survivin-positive. None of the hyperplasia cases showed any of these findings, so each marker had 100% specificity. Counting a case as positive if any one of the markers was abnormal found more of the cancers. All three markers together identified 92.6% of mesothelioma cases, with 95.9% accuracy, and Survivin with EZH2 alone gave the same results. The study did not look at asbestos exposure. The authors concluded that adding the three markers to the diagnostic panel would increase sensitivity, and that Survivin looked promising, especially combined with EZH2. They noted that the study covered only this cancer subtype and this one non-cancerous mimic.

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 immunohistochemical (tissue staining) study of archived biopsy samples, comparing two diagnostic groups
• Who was studied: 81 cases of pleural epithelioid mesothelioma (mean age 67.9 years) and 67 cases of reactive mesothelial hyperplasia (mean age 47.4 years). All were thoracoscopic pleural biopsies diagnosed January 2016 to December 2019, taken from the archives of Ain-Shams University Specialized Hospital and Ain-Shams University Hospitals, Cairo, Egypt.
• Exposure: No asbestos or other occupational or environmental exposure was studied. The study examined immunohistochemical staining for three nuclear markers: BAP1 (loss), EZH2 (high expression) and Survivin (positivity).
• Main results:
  • BAP1 loss was seen in 49 of 81 mesothelioma cases (60.5%). All 67 hyperplasia cases kept BAP1 expression.
  • High EZH2 expression was seen in 36 of 81 mesothelioma cases (44.4%) and in none of the 67 hyperplasia cases.
  • Survivin positivity was seen in 55 of 81 mesothelioma cases (67.9%). All 67 hyperplasia cases were Survivin-negative.
  • Used singly, each marker had 100% specificity. Sensitivities were 67.9% for Survivin, 60.5% for BAP1 loss and 44.4% for high EZH2.
  • All three markers combined gave the highest accuracy (95.9%) and sensitivity (92.6%). Survivin and EZH2 together gave the same figures, so adding BAP1 did not improve them.
  • Other pairs: high EZH2 and/or BAP1 loss had 85.2% sensitivity; Survivin-positive and/or BAP1 loss had 75.3% sensitivity.
  • Within the mesothelioma group, high EZH2 was inversely associated with BAP1 loss and with Survivin positivity, while BAP1 loss and Survivin positivity were directly associated.
  • The text reports no statistically significant relationships between the markers and features of the mesothelioma cases (growth pattern, grade, necrosis, nuclear atypia, IMIG stage).
• The authors' conclusion: The authors concluded that adding EZH2, Survivin and BAP1 to the diagnostic immunohistochemistry panel for distinguishing pleural epithelioid mesothelioma from reactive mesothelial hyperplasia would increase diagnostic sensitivity. They also concluded that Survivin has promising potential, especially when combined with EZH2.
• Limitations the authors state:
  • The study included only pleural epithelioid mesothelioma and reactive mesothelial hyperplasia. The authors said more studies are needed on other mesothelioma subtypes, other benign mesothelial lesions, other pleural tumors and metastatic tumors.

Topics

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

Medical terms in this study, explained in our Lexicon: BAP1, Epithelioid, Mesothelioma, Reactive Mesothelial Hyperplasia, Pleural Mesothelioma, Pathology.

Related studies

• Highly expressed EZH2 in combination with BAP1 and MTAP loss, as detected by immunohistochemistry, is useful for differentiating malignant pleural mesothelioma from reactive mesothelial hyperplasia — M. Yoshimura, Y. Kinoshita, et al. (2019)
• Diagnostic utility of BAP1 and EZH2 expression in malignant mesothelioma — A. Shinozaki-Ushiku, T. Ushiku, 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)
• How useful is GLUT-1 in differentiating mesothelial hyperplasia and fibrosing pleuritis from epithelioid and sarcomatoid mesotheliomas? An international collaborative study — A.N. Husain, M.K. Mirza, et al. (2014)
• Use of Anti-Noxa Antibody for Differential Diagnosis between Epithelioid Mesothelioma and Reactive Mesothelial Hyperplasia — K. Kushitani, V.J. Amatya, et al. (2016)
• Utility of Survivin, BAP1, and Ki-67 immunohistochemistry in distinguishing epithelioid mesothelioma from reactive mesothelial hyperplasia — K. Kushitani, V.J. Amatya, et al. (2018)

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