IDH-Mutation Is a Weak Predictor of Long-Term Survival in Glioblastoma Patients

PLoS One. 2015 Jul 9;10(7):e0130596. doi: 10.1371/journal.pone.0130596. eCollection 2015.

Abstract

Background: A very small proportion of patients diagnosed with glioblastoma (GBM) survive more than 3 years. Isocitrate dehydrogenase 1 or 2 (IDH1/2) mutations define a small subgroup of GBM patients with favourable prognosis. However, it remains controversial whether long-term survivors (LTS) are found among those IDH1/2 mutated patients.

Methods: We retrospectively analyzed 207 GBM patients followed at Lariboisière Hospital (Paris) between 2005 and 2010. Clinical parameters were obtained from medical records. Mutations of IDH1/2 were analyzed in these patients, by immunohistochemistry for the R132H mutation of IDH1 and by high-resolution melting-curve analysis, followed by Sanger sequencing for IDH1 and IDH2 exon 4 mutations. Mutation rates in LTS and non-LTS groups were compared by Chi square Pearson test.

Results: Seventeen patients with survival >3 years were identified (8.2% of the total series). The median overall survival in long-term survivors was 4.6 years. Subgroup analysis found that the median age at diagnosis was significantly higher for non long-term survivors (non-LTS) compared to LTS (60 versus 51 years, p <0.03). The difference in the rate of IDH mutation between non-LTS and LTS was statistically not significant (1.16% versus 5.9%, p = 0.144). Among LTS, 10 out of 16 tumors presented a methylation of MGMT promoter.

Conclusions: This study confirms that long-term survival in GBM patients is if at all only weakly correlated to IDH-mutation.

MeSH terms

  • Adult
  • Aged
  • Brain Neoplasms / enzymology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / therapy
  • Chi-Square Distribution
  • DNA Methylation
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • Female
  • Glioblastoma / enzymology
  • Glioblastoma / genetics*
  • Glioblastoma / therapy
  • Humans
  • Immunohistochemistry
  • Isocitrate Dehydrogenase / genetics*
  • Isocitrate Dehydrogenase / metabolism
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Mutation*
  • Outcome Assessment, Health Care / methods
  • Predictive Value of Tests
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Retrospective Studies
  • Survival Analysis
  • Survivors / statistics & numerical data*
  • Time Factors
  • Tumor Suppressor Proteins / genetics

Substances

  • Tumor Suppressor Proteins
  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human
  • DNA Modification Methylases
  • MGMT protein, human
  • DNA Repair Enzymes

Grants and funding

The authors have no support or funding to report.