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.

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Serval ID
serval:BIB_6613022C4BFB
Type
Article: article from journal or magazin.
Collection
Publications
Institution
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.
Journal
Acta Neuropathologica
Author(s)
Hegi M.E., Janzer R.C., Lambiv W.L., Gorlia T., Kouwenhoven M.C., Hartmann C., von Deimling A., Martinet D., Besuchet Schmutz N., Diserens A.C., Hamou M.F., Bady P., Weller M., van den Bent M.J., Mason W.P., Mirimanoff R.O., Stupp R., Mokhtari K., Wesseling P., European Organisation for Research, Treatment of Cancer Brain Tumour
Working group(s)
Radiation Oncology Groups, National Cancer Institute of Canada Clinical Trials Group
Contributor(s)
European Organisation for Research, Treatment of Cancer Brain Tumour
ISSN
1432-0533 (Electronic)
ISSN-L
0001-6322
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
123
Number
6
Pages
841-852
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't Publication
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.
Keywords
Adolescent, Adult, Aged, Brain Neoplasms/genetics, Brain Neoplasms/pathology, Chemoradiotherapy, Clinical Trials, Phase III as Topic, DNA Methylation, Dacarbazine/analogs & derivatives, Dacarbazine/therapeutic use, Female, Glioblastoma/genetics, Glioblastoma/pathology, Humans, Male, Middle Aged, Mutation, Oligodendroglioma/genetics, Oligodendroglioma/pathology, Prognosis, Receptor, Epidermal Growth Factor/genetics, Receptor, Epidermal Growth Factor/metabolism, Survival Analysis, Treatment Outcome, Young Adult
Pubmed
Web of science
Open Access
Yes
Create date
25/10/2012 16:03
Last modification date
01/10/2019 6:18
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