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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.
MedLine Citation:
PMID:  22249618     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
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:
Monika E Hegi; Robert-Charles Janzer; Wanyu L Lambiv; Thierry Gorlia; Mathilde C M Kouwenhoven; Christian Hartmann; Andreas von Deimling; Danielle Martinet; Nathalie Besuchet Schmutz; Annie-Claire Diserens; Marie-France Hamou; Pierre Bady; Michael Weller; Martin J van den Bent; Warren P Mason; René-Olivier Mirimanoff; Roger Stupp; Karima Mokhtari; Pieter Wesseling
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-1-15
Journal Detail:
Title:  Acta neuropathologica     Volume:  -     ISSN:  1432-0533     ISO Abbreviation:  -     Publication Date:  2012 Jan 
Date Detail:
Created Date:  2012-1-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0412041     Medline TA:  Acta Neuropathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland, Monika.Hegi@chuv.ch.
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