Journal Article

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

Amelot, Aymeric, De Cremoux, Patricia, Quillien, Véronique, Mandonnet, Emmanuel, Carpentier, Antoine F., Lehmann-Che, Jacqueline, Froelich, Sébastien, George, Bernard, Polivka, Marc, Adle-Biassette, Homa, Françoise, Laurence

2015

Overview

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

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adult / Aged / Analysis / Biochemistry / Brain cancer / Brain Neoplasms - enzymology / Brain Neoplasms - genetics / Brain Neoplasms - therapy / Chi-Square Distribution / Chi-square test / Deoxyribonucleic acid / DNA / DNA Methylation / DNA Modification Methylases - genetics / DNA Repair Enzymes - genetics / Enzymes / Female / Genetic aspects / Glioblastoma / Glioblastoma - enzymology / Glioblastoma - genetics / Glioblastoma - therapy / Glioblastomas / Humans / Immunohistochemistry / Isocitrate dehydrogenase / Isocitrate Dehydrogenase - genetics / Isocitrate Dehydrogenase - metabolism / Life Sciences / Male / Medical records / Methylation / Middle Aged / Multivariate Analysis / Mutation / Mutation rates / Nervous system / Neurosurgery / Oncology / Outcome Assessment (Health Care) - methods / Pathology / Patient outcomes / Patients / Predictive Value of Tests / Prognosis / Promoter Regions, Genetic - genetics / Retrospective Studies / Sequences / Statistical analysis / Studies / Survival / Survival Analysis / Survivors - statistics & numerical data / Time Factors / Tumor Suppressor Proteins - genetics / Tumors