MGMT methylation correlates with melphalan pelvic perfusion survival in stage III melanoma patients: A pilot study

Stefano Guadagni, Giammaria Fiorentini, Marco Clementi, Giancarlo Palumbo, Francesco Masedu, Marcello Deraco, Giovanni De Manzoni, Alessandro Chiominto, Marco Valenti, Cristina Pellegrini

Research output: Contribution to journalArticlepeer-review

Abstract

Approximately 25% of melanoma patients with locoregional metastases are nonresponsive to new molecular target therapy and immunotherapy. When metastases are located in the pelvis, melphalan hypoxic perfusion can be an optional treatment. Because methylation of MGMT promoter increases the efficacy of alkylating agents, studies on melanoma outcome of patients treated with melphalan regional chemotherapy should consider this epigenetic change. This study aims to evaluate whether the survival of stage III melanoma patients treated with melphalan regional chemotherapy may be correlated with MGMT methylation status. The metastatic tissues of 27 stage III melanoma patients with locoregional metastases located in the pelvis subjected to melphalan hypoxic pelvic perfusion were examined. The methylation status of the MGMT promoter was investigated by MS-MLPA probes analysis and the presence of the BRAF V600E mutation was analyzed by CAST-PCR. The median survival times were estimated using the Kaplan-Meier curves and were stratified according to the clinicopathological characteristics of patients and lesions. The overall median survival time was 17 months. The 1-year, 3-year, and 5-year survival rates were 66.7, 18.5, and 7.4%, respectively. Disease stage, burden, and percentage of MGMT methylation significantly affected survival. We estimated an MGMT promoter methylation cut-off of at least 14%, which was significantly associated with a longer survival after melphalan regional chemotherapy. Our data suggest that MGMT promoter methylation could be an important factor in determining which melanoma patients should receive melphalan regional chemotherapy, but its prognostic significance in the routine clinical setting needs to be clarified in a larger study.

Original languageEnglish
Pages (from-to)439-447
Number of pages9
JournalMelanoma Research
Volume27
Issue number5
DOIs
Publication statusPublished - Jan 1 2017

Keywords

  • Melanoma
  • Melphalan
  • Methylation
  • MGMT
  • Pelvis
  • Perfusion

ASJC Scopus subject areas

  • Oncology
  • Dermatology
  • Cancer Research

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