Prognostic significance of MGMT gene promoter methylation in differently treated metastatic melanomas

Aims: The methylation status of the MGMT gene promoter,considered of prognostic significance by enhancing chemosensitivityto alkylating drugs in gliomas and melanomas, wasevaluated in a series of primary melanomas and metastasesof patients treated with different therapies, to identify anycorrelation with the patients’ outcome or response to differenttherapeutic regimens.Methods: Twenty-nine primary melanomas and 74 metastases,collected from 52 patients, were assessed forMGMT gene promoter methylation using a standardmethylation specific PCR-based method. All materials wereformalin fixed and paraffin embedded.Results: One of 29 primary melanomas (3.4%) and 22 of74 metastases (29.7%) showed MGMT gene promotermethylation. MGMT methylation was more frequent invisceral (17/40, 42.5%) than in cutaneous/lymph nodemetastases (5/34, 14.7%) ( p¼0.019). Both disease free(DFS) and overall survival (OS) were significantly longerin patients with methylated metastases ( p¼0.009 andp¼0.007, respectively). No correlations were found amongmethylation, therapeutic regimens and DFS or OS.Conclusions: MGMTmethylation appears to be a late event inthe biological history of melanoma and is more frequentlyseen in visceral metastases. The MGMT gene promotermethylation in metastatic disease is associated with longersurvival, irrespective of therapy. Thus it could be considereda prognostic factor in metastatic melanoma.