title: Prognostic value of MGMT promoter methylation in glioblastoma patients treated with temozolomide-based chemoradiation: a Portuguese multicentre study.
abstract: Glioblastoma (GBM) is the most common and aggressive primary brain tumor. The identification of novel molecular prognostic markers of GBM has recently been an area of great interest in neuro-oncology. The methylation status of the MGMT gene promoter is currently a promising molecular prognostic marker, but some controversial data have precluded its clinical use. We analyzed MGMT methylation by methylation-specific PCR in 90 GBM patients from four Portuguese hospitals, uniformly treated with radiotherapy combined with concomitant and adjuvant temozolomide (Stupp protocol). The Kaplan-Meier method was used to construct survival curves, and the log-rank test and a Cox-regression model were used to analyze patient survival. The methylation status of MGMT was successfully determined in 89% (80/90) of the tumors. The frequency of tumoral MGMT promoter methylation was 47.5%. The median overall survivals (OSs) were 16 months (95% CI 12.2-19.8) and 13 months (95% CI 13.3-18.7) for patients whose tumors had a methylated or unmethylated MGMT, respectively. Univariate and multivariate analyses did not show any statistically significant association between MGMT methylation status and patient OS (P=0.583 by the log-rank test; P=0.617 by the Cox-regression test) or progression-free survival (P=0.775 by the log-rank test; P=0.691 by the Cox-regression test). None of the patient clinical features were significantly correlated with survival. This is the first study to report the frequency of MGMT methylation among Portuguese GBM patients. Our data did not show statistically significant associations between MGMT promoter methylation and the outcome of GBM patients treated with temozolomide. Additional robust prospective studies are warranted to clarify whether the MGMT status should be used in clinical decisions.
authors.affiliation: Life and Health Sciences Research Institute (ICVS), Health Sciences School, University of Minho, Braga, Portugal.
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Costa
authors.forename: Cláudia
authors.initials: C
authors.lastname: Caeiro
authors.forename: Inês
authors.initials: I
authors.lastname: Guimarães
authors.forename: Olga
authors.initials: O
authors.lastname: Martinho
authors.forename: Teresa
authors.initials: T
authors.lastname: Jaraquemada
authors.forename: Isabel
authors.initials: I
authors.lastname: Augusto
authors.forename: Lígia
authors.initials: L
authors.lastname: Castro
authors.forename: Lígia
authors.initials: L
authors.lastname: Osório
authors.forename: Paulo
authors.initials: P
authors.lastname: Linhares
authors.forename: Mrinalini
authors.initials: M
authors.lastname: Honavar
authors.forename: Mário
authors.initials: M
authors.lastname: Resende
authors.forename: Fátima
authors.initials: F
authors.lastname: Braga
authors.forename: Ana
authors.initials: A
authors.lastname: Silva
authors.forename: Fernando
authors.initials: F
authors.lastname: Pardal
authors.forename: Júlia
authors.initials: J
authors.lastname: Amorim
authors.forename: Rui
authors.initials: R
authors.lastname: Nabiço
authors.forename: Rui
authors.initials: R
authors.lastname: Almeida
authors.forename: Carlos
authors.initials: C
authors.lastname: Alegria
authors.forename: Manuel
authors.initials: M
authors.lastname: Pires
authors.forename: Célia
authors.initials: C
authors.lastname: Pinheiro
authors.forename: Ernesto
authors.initials: E
authors.lastname: Carvalho
authors.forename: José M
authors.initials: JM
authors.lastname: Lopes
authors.forename: Paulo
authors.initials: P
authors.lastname: Costa
authors.forename: Margarida
authors.initials: M
authors.lastname: Damasceno
authors.forename: Rui M
authors.initials: RM
authors.lastname: Reis
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D003131:Combined Modality Therapy; D019175:DNA Methylation; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005909:Glioblastoma / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics*; D011174:Portugal; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011879:Radiotherapy Dosage; D015996:Survival Rate; D000077204:Temozolomide; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D003606:Dacarbazine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D000077204:Temozolomide