Diagnostic utility of <scp>BAP</scp>1 and <scp>EZH</scp>2 expression in malignant mesothelioma

Aims Malignant mesothelioma is a highly aggressive cancer that is usually diagnosed at advanced stages; thus, highly sensitive and specific markers are necessary for its early definitive diagnosis. The aim of this study was to evaluate the diagnostic utility and prognostic significance of BAP 1 and EZH 2 in malignant mesothelioma. Methods and results The expression of BAP 1 and EZH 2 was investigated by immunohistochemistry in 32 malignant mesotheliomas and 44 benign mesothelial proliferative lesions, including well‐differentiated papillary mesothelioma ( n = 4), mesothelial inclusion cyst ( n = 22), and reactive mesothelial hyperplasia ( n = 18). BAP 1 loss and high EZH 2 expression were observed in 17 (53%) and 22 (66%) malignant mesothelioma cases, respectively, whereas none of the benign lesions showed BAP 1 loss or high EZH 2 expression. The combination of BAP 1 loss and high EZH 2 expression as markers to differentiate epithelioid/biphasic malignant mesothelioma from benign mesothelial lesions was highly sensitive (90%) and specific (100%). There were no statistically significant associations between parameters such as age and sex of patients, tumour location, asbestos exposure, treatment, histology, and BAP 1 or EZH 2 expression. Survival analysis revealed that BAP 1 loss, but not high EZH 2 expression, was associated with a better prognosis. Conclusions BAP 1 loss and high EZH 2 expression were highly specific to malignant mesothelioma in differentiating it from benign mesothelial proliferations, and the combination of these two markers improved the diagnostic accuracy.