title: The combined EGFR protein expression analysis refines the prognostic value of the MGMT promoter methylation status in glioblastoma.
abstract: OBJECTIVE
  To investigate the combined prognostic value of the EGFR expression level and the MGMT promoter methylation status in Glioblastoma (GB).
  
  
  METHODS
  We assessed the EGFR protein expression level by immune-histochemical (IHC) evaluation and the MGMT promoter methylation status by Polymerase Chain Reaction (PCR) in 169 patients affected by GB. We assessed the prognostic significance of combined MGMT methylation status and EGFR expression level in terms of Overall Survival (OS) with univariate and multivariate analysis, and validated this finding using an external data set of GB patient.
  
  
  RESULTS
  Clustering survival analysis for the methylation status of MGMT (methMGMT/unmethMGMT) and EGFR expression (High EGFR: H-EGFR; Low EGFR: L-EGFR), identified three different prognostic groups (p=0.001), as follows. Patients with unmethMGMT/H-EGFR had the shortest survival time (median OS: 5 months) and patients co-expressing methMGMT/L-EGFR had the best prognosis (median OS: 35 months), as compared to the other two sub-groups (methMGMT/H-EGFR; unmethMGMT/L-EGFR), which had respectively median OSs of 11 and 12 months. The combined MGMT methylation and EGFR amplification status analysis showed a similar prognostic impact in an independent series, which we used for validation (p=0.001).
  
  
  CONCLUSIONS
  The EGFR expression evaluation refines the prognostic value of MGMT methylation status in GBs.
authors.affiliation: IstitutoToscanoTumori, Firenze, Italy; Unit of Radiation Oncology, University Hospital of Siena, Siena, Italy. Electronic address: paolo-tini@libero.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Tini
authors.affiliation: IstitutoToscanoTumori, Firenze, Italy; Radiation Oncology, Department of Medicine, Surgery and Neurological Sciences, University of Siena, Siena, Italy.
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Pastina
authors.affiliation: IstitutoToscanoTumori, Firenze, Italy; Radiation Oncology, Department of Medicine, Surgery and Neurological Sciences, University of Siena, Siena, Italy.
authors.forename: Valerio
authors.initials: V
authors.lastname: Nardone
authors.affiliation: IstitutoToscanoTumori, Firenze, Italy; Unit of Radiation Oncology, University Hospital of Siena, Siena, Italy.
authors.forename: Lucio
authors.initials: L
authors.lastname: Sebaste
authors.affiliation: IstitutoToscanoTumori, Firenze, Italy; Radiation Oncology, Department of Medicine, Surgery and Neurological Sciences, University of Siena, Siena, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Toscano
authors.affiliation: IstitutoToscanoTumori, Firenze, Italy; Pathological Anatomy, Department of Medicine, Surgery and Neurological Sciences, University of Siena, Siena, Italy.
authors.forename: Clelia
authors.initials: C
authors.lastname: Miracco
authors.affiliation: IstitutoToscanoTumori, Firenze, Italy; Unit of Neuroradiology, University Hospital of Siena, Siena, Italy.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Cerase
authors.affiliation: IstitutoToscanoTumori, Firenze, Italy; Unit of Radiation Oncology, University Hospital of Siena, Siena, Italy; Radiation Oncology, Department of Medicine, Surgery and Neurological Sciences, University of Siena, Siena, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Pirtoli
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000401:mortality; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000378:metabolism*; D045643:DNA Repair Enzymes / Q000378:metabolism*; D066246:ErbB Receptors / Q000378:metabolism*; D015870:Gene Expression; D005909:Glioblastoma / Q000175:diagnosis* / Q000401:mortality; D006801:Humans; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; D045643:DNA Repair Enzymes
keywords: EGFR; Glioblastoma; MGMT; Prognostic markers; Radiotherapy; Temozolomide