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

• Published in: PloS one Vol. 10; no. 7; p. e0130596
• Main Authors: Amelot, Aymeric, De Cremoux, Patricia, Quillien, Véronique, Polivka, Marc, Adle-Biassette, Homa, Lehmann-Che, Jacqueline, Françoise, Laurence, Carpentier, Antoine F, George, Bernard, Mandonnet, Emmanuel, Froelich, Sébastien
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 09.07.2015; Public Library of Science (PLoS)
• Subjects: 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; Immunohistochemistry; Multivariate Analysis; Predictive Value of Tests; Prognosis; Outcome Assessment (Health Care); Humans; Middle Aged; Glioblastoma; Genetic; Male; Brain Neoplasms; DNA Methylation; Time Factors; DNA Modification Methylases; Adult; Female; Retrospective Studies; Isocitrate Dehydrogenase; Promoter Regions; Survivors; Chi-Square Distribution; DNA Repair Enzymes; Survival Analysis; Aged; Mutation; Tumor Suppressor Proteins
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0130596

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.