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.
Highlights
Pleural malignant mesothelioma poses a diagnostic challenge that may cause late diagnosis at an advanced stage
Survivin expression is said to be significantly higher in epithelioid mesothelioma (EM) than in nonneoplastic pleural tissue, but its diagnostic utility as an immunohistochemical marker has not been thoroughly investigated in this field
All of Survivin positivity, BRCA1-associated protein 1 (BAP1) loss, and high expression of EZH2 expressed in cases of EM had 100% specificity, and their sensitivities were 67.9, 60.5, and 44.4%, respectively
Summary
Pleural malignant mesothelioma poses a diagnostic challenge that may cause late diagnosis at an advanced stage. BRCA1-associated protein 1 (BAP1) is a newly identified diagnostic marker whose loss is specific to malignant mesothelioma [2, 3]. BAP1 loss is caused by mutations, deletions or epigenetic silencing of BAP1 in both familial and sporadic malignant mesothelioma. It encodes ubiquitin C-terminal hydrolase that may have a role in keeping the appropriate ubiquitination status of target histones. BAP1 is a newly identified diagnostic marker whose loss is specific to malignant mesothelioma. 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
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