1. 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
- Author
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Mathilde C.M. Kouwenhoven, Karima Mokhtari, René-Olivier Mirimanoff, Marie-France Hamou, Christian Hartmann, Danielle Martinet, Pieter Wesseling, Roger Stupp, A. von Deimling, M. J. van den Bent, Michael Weller, N Besuchet Schmutz, Wanyu L. Lambiv, Robert-Charles Janzer, Thierry Gorlia, Annie-Claire Diserens, Monika E. Hegi, Pierre Bady, Warren P. Mason, Pathology, CCA - Disease profiling, University of Zurich, Hegi, M E, Neurology, Radiation Oncology Groups, National Cancer Institute of Canada Clinical Trials Group, European Organisation for, Research, and Treatment of Cancer Brain, Tumour
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Male ,Oncology ,Pathology ,medicine.medical_treatment ,2804 Cellular and Molecular Neuroscience ,Central Pathology Review ,0302 clinical medicine ,Brain Neoplasms ,Chemoradiotherapy ,Middle Aged ,Prognosis ,Translational research Tissue engineering and pathology [ONCOL 3] ,3. Good health ,Dacarbazine ,ErbB Receptors ,Treatment Outcome ,2728 Neurology (clinical) ,030220 oncology & carcinogenesis ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,IDH1 ,Adolescent ,Oligodendroglioma ,610 Medicine & health ,Pathology and Forensic Medicine ,Young Adult ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Internal medicine ,Temozolomide ,medicine ,Humans ,Clinical significance ,Aged ,Brain Neoplasms/genetics ,Brain Neoplasms/pathology ,Clinical Trials, Phase III as Topic ,DNA Methylation ,Dacarbazine/analogs & derivatives ,Dacarbazine/therapeutic use ,Glioblastoma/genetics ,Glioblastoma/pathology ,Mutation ,Oligodendroglioma/genetics ,Oligodendroglioma/pathology ,Receptor, Epidermal Growth Factor/genetics ,Receptor, Epidermal Growth Factor/metabolism ,Survival Analysis ,Chemotherapy ,business.industry ,medicine.disease ,10040 Clinic for Neurology ,nervous system diseases ,2734 Pathology and Forensic Medicine ,Clinical trial ,Component (group theory) ,Neurology (clinical) ,Glioblastoma ,business ,030217 neurology & neurosurgery - Abstract
Item does not contain fulltext 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. 01 juni 2012
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- 2012
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