Clinical significance of c-MYC and EZH-2 expressions and loss of merlin andBAP-1

Aim: Malignant mesothelioma (MM) is an aggressive tumor originating from pleural, peritoneal or perikardiyal cavities. Although the most powerful prognostic factors are stage and histology in MM, there is need to find prognostic and/or predicitve factors for MM for precision medicine. The aim of this study is to explore the association between demographic variables and also prognostic significance of BAP-1, EZH-2, c-MYC and Merlin in MM. Patients and methods: 75 patients with MM followed by Çukurova University Faculty of Medicine Dept of Oncology were evaluated retrospectively. Demographic properties of the 75 patients including asbest exposure, smoker history, tumor localization, histopathologic type, treatment modalities, ECOG performance status and disease stage were evaluated. BAP-1, EZH-2, c-MYC and Merlin expressions were evaluated by immunohistochemistry in 67 cases and expression levels and/or loss of expression and results were compared with survival times. IBM SPSS version 20.0 was used for statistical analyses. Findings: Female/male ratio was 42/32, mean age was 60 ± 10,8. The majority of the cases had epitheloid type MM (60 cases), 12 had biphasic and 3 had sarcomatoid type. Median overall survival was longer in women, in cases with early stage disease, in non-smokers, in cases with good performance status and in cases with epitheloid type MM. BAP-1 loss was not found to be associated with progression free survival and overall survival. Merlin loss was not found to be associated with overall and progression free survival. Strong EZH-2 expression with two cut off levels was found to be associated with shorter overall survival. Strong c-MYC expression was found to be associated with shorter overall survival. Double expression for EZH-2 and c-MYC was found to be asociated with shortest survival while double negative cases had shortest survival. Histologic subtype, stage, ECOG performance status and EZH-2 were found to be prognostic in multivariate analysis. Conclusion: BAP-1, EZH-2, c-MYC and Merlin expressions may be detected by immunohistochemistry in biopsy samples or surgical specimens. Especially EZH-2 and c-MYC expressions have been found to be associated with shorter progression and overall survival times. Targeting EZH-2 and/or c-MYC may be an important therapeutic choice in cases with MM. We need further studies to validate these results Key words: Malignant mesothelioma, BAP-1, EZH-2, Merlin, c-MYC, survival