title: Combining two biomarkers, IDH1/2 mutations and 1p/19q codeletion, to stratify anaplastic oligodendroglioma in three groups: a single-center experience.
abstract: IDH1/2 mutations and 1p/19q codeletion occur frequently in anaplastic gliomas and are prognostic factors. We combined these two biomarkers to stratify patients treated for anaplastic oligodendroglioma (AO). 43 consecutive WHO AO were selected. We combined immunohistochemistry (IHC) with the monoclonal antibody mIDH1R132H and DNA sequencing of IDH1 and IDH2 genes. Fluorescence in situ hybridization was carried out to evaluate 1p/19q codeletion. These biomarkers were correlated with progression-free survival (PFS) and overall survival (OS). IDH1/IDH2 mutations occurred in 23/43 (54 %) patients: 20/43 IDH1-R132H mutation in IHC, 2/43 IDH1-R132G mutation and 1/43 IDH2-R172K mutation identified by DNA sequencing. 1p/19q codeletion was detected for 23/43 patients. With median follow-up of 19 months (range 1.4-128), median PFS and OS were 22 and 35 months respectively. IDH1/IDH2 mutations were strongly associated with improved PFS and OS: 5-year PFS was 86 versus 6 % and 5-year OS was 91 versus 9 % for patients with IDH1/IDH2 mutations versus wild-type IDH respectively. In multivariate analyses, IDH1/IDH2 mutations and 1p/19q loss were independent prognostic factors. Three groups with distinct prognostic features were identified: patients with IDH1/2 mutations and 1p/19q loss (median PFS, median OS not reached), patients with IDH1/2 mutations or 1p/19q loss (median PFS: 22 months, median OS: 30 months), and patients without IDH1/2 mutations nor 1p/19q loss with a bad prognosis (median PFS: 8.6 months, median OS: 9.9 months). Combining two biomarkers, IDH1/2 and 1p/19q codeletion, makes it possible to stratify AO in three groups with very distinct prognostic features.
authors.affiliation: Medical Oncology Department, Institut de Cancérologie de l'Ouest, Centre René Gauducheau, 11 Boulevard Jacques Monod, 44800, Saint-Herblain, Nantes, France. jean-sebastien.frenel@ico.unicancer.fr
authors.forename: J S
authors.initials: JS
authors.lastname: Frenel
authors.forename: C
authors.initials: C
authors.lastname: Leux
authors.forename: D
authors.initials: D
authors.lastname: Loussouarn
authors.forename: A-G
authors.initials: AG
authors.lastname: Le Loupp
authors.forename: F
authors.initials: F
authors.lastname: Leclair
authors.forename: M
authors.initials: M
authors.lastname: Aumont
authors.forename: A
authors.initials: A
authors.lastname: Mervoyer
authors.forename: S
authors.initials: S
authors.lastname: Martin
authors.forename: M G
authors.initials: MG
authors.lastname: Denis
authors.forename: M
authors.initials: M
authors.lastname: Campone
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality; D002872:Chromosome Deletion; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007521:Isocitrate Dehydrogenase / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009837:Oligodendroglioma / Q000235:genetics* / Q000401:mortality; D016016:Proportional Hazards Models
chemical_list: C538784:IDH2 protein, human; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human