32nd EORTC-NCI-AACR symposium Molecular Targets and Cancer Therapeutics, Brussels, Belçika, 24 - 25 Ekim 2020, cilt.138, ss.42
Aim: Malignant mesothelioma (MM) is an aggressive tumor originating from pleural, peritoneal or perikardiyal cavities. Although the most powerful prognostic factors are stage and histologic sybtypes there is need to find prognostic and/or predicitve factors for targeted treatment. The aim of this study is to explore the association between known prognostic factors and also prognostic significance of EZH-2, c-MYC and Merlin in MM.
Patients and methods: Sixty seven patients with MM followed by Çukurova University Faculty of Medicine Dept of Oncology were evaluated retrospectively. Demographic properties of the 67 patients including asbest exposure, smoker history, tumor localization, histopathologic type, treatment modalities, ECOG performance status and disease stage were evaluated. EZH-2, c-MYC and Merlin expressions were evaluated by immunohistochemistry (IHC) Expression and/or loss of EZH-2, c-MYC and Merlin were compared with demographic/clinical findings and survival times. IBM SPSS version 20.0 was used for statistical analyses. Cut off level for XH-2 was 30%. c-MYC and Merlin were evaluated according to staining intensity as weak (1-19%), moderate (20–59%), strong (60–100%).
Findings: Female/male ratio was 38/29, mean age was 60,3 ± 10,5. The majority of the cases had epitheloid type MM (54 cases), 11 had biphasic and 2 had sarcomatoid type. Median overall survival was longer in women, in early stage disease, in non-smokers, in good performance status and in cases with epitheloid type MM.
Merlin loss was not found to be associated with overall survival (OS) and progression free survival (PFS). Strong EZH-2 expression with 30% cut off level was found to be associated with shorter overall survival. Strong c-MYC expression was found to be associated with shorter overall survival. Interestingly double expression for EZH-2 and c-MYC was found to be asociated with shortest survival while double negative cases had longest survival. Histologic subtype, stage, ECOG performance status and EZH-2 were found to be prognostic in multivariate analysis.
Conclusion: EZH-2, c-MYC and Merlin expressions were detected by IHC in biopsy specimens. EZH-2 and c-MYC expressions were found to be associated with shorter PFS and OS times. However our results must be validated with further studies. It is well known that EZH-2 inhibitors and also c-MYC inhibitors have been found to be successfull in some types of tumors. We can propose that inhibition of EZH-2 and/or c-MYC may be an important therapeutic alternative in cases with MM.