title: Presence of an oligodendroglioma-like component in newly diagnosed glioblastoma identifies a pathogenetically heterogeneous subgroup and lacks prognostic value: central pathology review of the EORTC_26981/NCIC_CE.3 trial.
abstract: Glioblastoma (GBM) is a morphologically heterogeneous tumor type with a median survival of only 15 months in clinical trial populations. However, survival varies greatly among patients. As part of a central pathology review, we addressed the question if patients with GBM displaying distinct morphologic features respond differently to combined chemo-radiotherapy with temozolomide. Morphologic features were systematically recorded for 360 cases with particular focus on the presence of an oligodendroglioma-like component and respective correlations with outcome and relevant molecular markers. GBM with an oligodendroglioma-like component (GBM-O) represented 15% of all confirmed GBM (52/339) and was not associated with a more favorable outcome. GBM-O encompassed a pathogenetically heterogeneous group, significantly enriched for IDH1 mutations (19 vs. 3%, p = 0.003) and EGFR amplifications (71 vs. 48%, p = 0.04) compared with other GBM, while co-deletion of 1p/19q was found in only one case and the MGMT methylation frequency was alike (47 vs. 46%). Expression profiles classified most of the GBM-O into two subtypes, 36% (5/14 evaluable) as proneural and 43% as classical GBM. The detection of pseudo-palisading necrosis (PPN) was associated with benefit from chemotherapy (p = 0.0002), while no such effect was present in the absence of PPN (p = 0.86). In the adjusted interaction model including clinical prognostic factors and MGMT status, PPN was borderline nonsignificant (p = 0.063). Taken together, recognition of an oligodendroglioma-like component in an otherwise classic GBM identifies a pathogenetically mixed group without prognostic significance. However, the presence of PPN may indicate biological features of clinical relevance for further improvement of therapy.
authors.affiliation: Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland. Monika.Hegi@chuv.ch
authors.forename: Monika E
authors.initials: ME
authors.lastname: Hegi
authors.forename: Robert-Charles
authors.initials: RC
authors.lastname: Janzer
authors.forename: Wanyu L
authors.initials: WL
authors.lastname: Lambiv
authors.forename: Thierry
authors.initials: T
authors.lastname: Gorlia
authors.forename: Mathilde C M
authors.initials: MC
authors.lastname: Kouwenhoven
authors.forename: Christian
authors.initials: C
authors.lastname: Hartmann
authors.forename: Andreas
authors.initials: A
authors.lastname: von Deimling
authors.forename: Danielle
authors.initials: D
authors.lastname: Martinet
authors.forename: Nathalie
authors.initials: N
authors.lastname: Besuchet Schmutz
authors.forename: Annie-Claire
authors.initials: AC
authors.lastname: Diserens
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Hamou
authors.forename: Pierre
authors.initials: P
authors.lastname: Bady
authors.forename: Michael
authors.initials: M
authors.lastname: Weller
authors.forename: Martin J
authors.initials: MJ
authors.lastname: van den Bent
authors.forename: Warren P
authors.initials: WP
authors.lastname: Mason
authors.forename: René-Olivier
authors.initials: RO
authors.lastname: Mirimanoff
authors.forename: Roger
authors.initials: R
authors.lastname: Stupp
authors.forename: Karima
authors.initials: K
authors.lastname: Mokhtari
authors.forename: Pieter
authors.initials: P
authors.lastname: Wesseling
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D059248:Chemoradiotherapy; D017326:Clinical Trials, Phase III as Topic; D019175:DNA Methylation; D003606:Dacarbazine / Q000031:analogs & derivatives / Q000627:therapeutic use; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005909:Glioblastoma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009837:Oligodendroglioma / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D011379:Prognosis; D016019:Survival Analysis; D000077204:Temozolomide; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003606:Dacarbazine; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077204:Temozolomide