title: Prognostic significance of MGMT gene promoter methylation in differently treated metastatic melanomas.
abstract: OBJECTIVE
  The methylation status of the MGMT gene promoter, considered of prognostic significance by enhancing chemosensitivity to alkylating drugs in gliomas and melanomas, was evaluated in a series of primary melanomas and metastases of patients treated with different therapies, to identify any correlation with the patients' outcome or response to different therapeutic regimens.
  
  
  METHODS
  Twenty-nine primary melanomas and 74 metastases, collected from 52 patients, were assessed for MGMT gene promoter methylation using a standard methylation specific PCR-based method. All materials were formalin fixed and paraffin embedded.
  
  
  RESULTS
  One of 29 primary melanomas (3.4%) and 22 of 74 metastases (29.7%) showed MGMT gene promoter methylation. MGMT methylation was more frequent in visceral (17/40, 42.5%) than in cutaneous/lymph node metastases (5/34, 14.7%) (p = 0.019). Both disease free (DFS) and overall survival (OS) were significantly longer in patients with methylated metastases (p = 0.009 and p = 0.007, respectively). No correlations were found among methylation, therapeutic regimens and DFS or OS.
  
  
  CONCLUSIONS
  MGMT methylation appears to be a late event in the biological history of melanoma and is more frequently seen in visceral metastases. The MGMT gene promoter methylation in metastatic disease is associated with longer survival, irrespective of therapy. Thus it could be considered a prognostic factor in metastatic melanoma.
authors.affiliation: Department of Anatomic Pathology, Azienda Ospedaliero-Universitaria Policlinico, University of Modena and Reggio Emilia, Modena, Italy. cesinaro.annamaria@policlinico.mo.it
authors.forename: A M
authors.initials: AM
authors.lastname: Cesinaro
authors.forename: G
authors.initials: G
authors.lastname: Sartori
authors.forename: M
authors.initials: M
authors.lastname: Migaldi
authors.forename: L
authors.initials: L
authors.lastname: Schirosi
authors.forename: G
authors.initials: G
authors.lastname: Pellacani
authors.forename: G
authors.initials: G
authors.lastname: Collina
authors.forename: A
authors.initials: A
authors.lastname: Maiorana
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D003131:Combined Modality Therapy; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics* / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007558:Italy / Q000453:epidemiology; D053208:Kaplan-Meier Estimate; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008297:Male; D008545:Melanoma / Q000235:genetics / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D008875:Middle Aged; D011379:Prognosis; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012878:Skin Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000401:mortality / Q000628:therapy; D015996:Survival Rate; D016896:Treatment Outcome; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes