Prognostic Value of MGMT Promoter Methylation and TP53 Mutation in Glioblastomas Depends on IDH1 Mutation


Several molecular markers have been proposed as predictors of outcome in patients with glioblastomas.We investigated the prognostic significance of O6-methylguanine-DNA methyltransferase (MGMT) promotermethylation and TP53 mutation status dependent on isocitrate dehydrogenase 1 (IDH1) mutation in glioblastomapatients. A cohort of 78 patients with histologically confirmed glioblastomas treated with radiation therapy andchemotherapy were reviewed retrospectively. We evaluated the prognostic value of MGMT promoter methylationand TP53 mutation status with regard to progression-free survival (PFS) and overall survival (OS). It was revealedthat mutations in IDH1, promoter methylation of MGMT, TP53 mutation, age, Karnofsky performance status(KFS), and extension of resection were independent prognostic factors. In patients with an IDH1 mutation, thosewith an MGMT methylation were associated with longer PFS (p=0.016) and OS (p=0.013). Nevertheless, thepresence of TP53 mutation could stratify the PFS and OS of patients with IDH1 wild type (p=0.003 and 0.029respectively, log-rank). The MGMT promoter methylation and TP53 mutation were associated with a favorableoutcome of patients with and without mutant IDH1, respectively. The results indicate that glioblastomas withMGMT methylation or TP53 mutations have improved survival that may be influenced by IDH1 mutation status.