title: Tumour and serum MGMT promoter methylation and protein expression in glioblastoma patients.
abstract: BACKGROUND
  Methylation of the promoter of the MGMT gene and MGMT protein expression are recognized as predictive markers for response to alkylating chemotherapy in glioblastoma (GB).
  
  
  METHODS
  We have assessed MGMT methylation with the methylation-specific polymerase chain reaction (MSP) in tumor samples from 70 GB patients and in serum samples from 37 of these patients. We have also assessed MGMT protein expression by immunohistochemical (IHC) analysis in tissue samples from 63 of these patients.
  
  
  RESULTS
  We found concordance between MGMT methylation status in tissue and serum (Cohen's Kappa = 0.586; p<0.0001). MSP for detection of non-methylated MGMT promoter in serum showed a sensitivity of 95.4% and a specificity of 60%, while the IHC methylation test showed a low specificity (8.9%). Patients whose MGMT promoter was methylated in tissue attained longer progression-free and overall survival. In the multivariate analysis, serum MGMT promoter methylation emerged as an independent factor for longer progression-free and overall survival.
  
  
  CONCLUSIONS
  Serum-based MGMT methylation analysis offers a promising alternative to tumor-based MGMT analysis in cases where tissue samples are unavailable.
authors.affiliation: Medical Oncology Service, Catalan Institute of Oncology (ICO), Hospital Germans Trias i Pujol, Carretera Canyet s/n, Badalona, Barcelona, Spain. cbalana@iconcologia.net
authors.forename: Carmen
authors.initials: C
authors.lastname: Balańa
authors.forename: Cristina
authors.initials: C
authors.lastname: Carrato
authors.forename: José Luis
authors.initials: JL
authors.lastname: Ramírez
authors.forename: Andrés Felipe
authors.initials: AF
authors.lastname: Cardona
authors.forename: Mireia
authors.initials: M
authors.lastname: Berdiel
authors.forename: José Javier
authors.initials: JJ
authors.lastname: Sánchez
authors.forename: Miquel
authors.initials: M
authors.lastname: Tarón
authors.forename: Cristina
authors.initials: C
authors.lastname: Hostalot
authors.forename: Eva
authors.initials: E
authors.lastname: Musulen
authors.forename: Aurelio
authors.initials: A
authors.lastname: Ariza
authors.forename: Rafael
authors.initials: R
authors.lastname: Rosell
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics / Q000378:metabolism; D001774:Blood Chemical Analysis; D001932:Brain Neoplasms / Q000097:blood / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D019175:DNA Methylation / Q000502:physiology; D015254:DNA Modification Methylases / Q000032:analysis / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000032:analysis / Q000097:blood / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000097:blood / Q000235:genetics* / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000502:physiology; D012189:Retrospective Studies; D044967:Serum / Q000737:chemistry / Q000378:metabolism; D016019:Survival Analysis; D046888:Tissue Array Analysis; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000097:blood / 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