Validation of the new glioma WHO classification in the french POLA network: Analysis of 1041 cases.

Abstract

2015 Background: The upcoming WHO classification of gliomas will be refined taking into account the robust molecular alterations of gliomagenesis: the 1p19q codeletion and IDH1/2mutations. Methods: All cases of high-grade oligodendroglial tumors sent for central pathological review and included into the French nation-wide POLA network were reclassified according the upgrading of the 4th WHO classification that integrates pathological features and molecular data. Immunohistochemical expression of IDH1R132H, and ATRX, 1p19q codeletion, chromosome 7p gain and chromosome 10q loss by genomic-array and IDH1/2and histone K27M mutational statuses by sequencing were evaluated. Results: 1041 patients were included with a median age at diagnosis of 50.4 years (range, 17.1-84.4). Based on the new histo-molecular classification, diagnoses were: anaplastic oligodendroglioma with 1p19q codeletion (32.5%), anaplastic astrocytoma IDH mutated (IDHmt) (11.0%), anaplastic astrocytoma IDHwild-type (IDHwt) (5.3%), glioblastoma IDHmt (17.1%) and glioblastoma IDHwt (33.2%). Ten patients presented a midline tumor with the histone H3-K27M mutation. Both new and oldest WHO classifications were predictive for Progression-Free Survival (PFS) and Overall Survival (OS) but the new histo-molecular classification was more discriminant with higher hazard ratio for PFS (1.603, 1.848, 5.025 and 6.135 versus 1.495, 2.705, 2.799 and 4.933) and for OS (3.588, 3.493, 11.020 and 14.708 versus 2.259, 4.340, 4.214 and 7.534). Grading (III versus IV) was not prognostic for IDHmt non 1p19q codeleted gliomas in univariate analyses (PFS, p=0.5; OS, p=0.8) and multivariate analysis (adjusted by age, type of surgery and first line treatment: PFS, p=0.13; OS, p=0.38). Among anaplastic astrocytoma IDHwt, cases presenting with 7p gain and 10q loss (55%) had a worse prognosis that the others for PFS (p=0.027), suggesting that all anaplastic astrocytoma IDHwt should not be considered as glioblastoma IDHwt. Conclusions: WHO histo-molecular classification of gliomas presented with high predictive and discriminative value, allowing the validation of three main molecular subgroups for the future neuro-oncological trials.