Prognostic and predictive value of treatment response of EZH2 expression in melanoma patients at IV stage and evaluation of its relation with melanoma biological and clinical characteristics (PR.E.M.I.E.R. study)

Enhancer of zeste homolog 2 (EZH2), is the catalytic subunit of the polycomb 2 repressive complex (PRC2) with histone H3 methyltransferase function. EZH2 is a potential prognostic biomarker that predicts the aggressive clinical of neoplastic diseases. this is a retrospective exploratory clinical and translational study, on early stage and metastatic melanoma. Our aims are to correlate the immunohistochemical expression of EZH2 on primitive melanomas and metastatic melanoma lesions with histopathological parameters and melanoma TNM stage, and with the analysis of clinical / biological behavior in relation to the treatments performed. 89 patients were enrolled in this study. At diagnosis of primary melanoma, 32% patients were already in stage IV due to the presence of synchronous metastasis; 34% were in stage I or II, 34% were in stage III due to the presence of locoregional lymphnodes involvement. In stage I-II-III group, patients who develop metastasis during follow-up were 43 (48%) and patients who never develop metastasis were 17 (19%). E elevated EZH2 in the initial stages appears to be associated with a more aggressive disease with potential metastatic lymph node involvement or distant metastases ab initio. In metastatic setting, EZH2 3 seems to predict a greater activity of target therapies and EZH2 0 seems to predict a lower efficacy of ipilimumab, elements that can guide the choice of treatment between options such as BRAF + MEK inhibitors, AntiPD1 or AntiPD1+AntiCTLA4.