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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

Hegi, Monika ; Janzer, Robert-Charles ; Lambiv, Wanyu ; Gorlia, Thierry ; Kouwenhoven, Mathilde ; Hartmann, Christian ; von Deimling, Andreas ; Martinet, Danielle ; Besuchet Schmutz, Nathalie ; Diserens, Annie-Claire ; Hamou, Marie-France ; Bady, Pierre ; Weller, Michael ; van den Bent, Martin ; Mason, Warren ; Mirimanoff, René-Olivier ; Stupp, Roger ; Mokhtari, Karima ; Wesseling, Pieter

In: Acta Neuropathologica, 2012, vol. 123, no. 6, p. 841-852

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    Titre
    • 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
    Auteur
    • Hegi, Monika. Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
    • Janzer, Robert-Charles. Department of Pathology, Lausanne University Hospital, Lausanne, Switzerland
    • Lambiv, Wanyu. Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
    • Gorlia, Thierry. European Organisation for Research and Treatment of Cancer (EORTC) Headquaters, Brussels, Belgium
    • Kouwenhoven, Mathilde. Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
    • Hartmann, Christian. Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University, Heidelberg, Germany
    • von Deimling, Andreas. Department of Neuropathology, Institute of Pathology, Ruprecht-Karls-University, Heidelberg, Germany
    • Martinet, Danielle. Department of Medical Genetics, Lausanne University Hospital, Lausanne, Switzerland
    • Besuchet Schmutz, Nathalie. Department of Medical Genetics, Lausanne University Hospital, Lausanne, Switzerland
    • Diserens, Annie-Claire. Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
    • Hamou, Marie-France. Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
    • Bady, Pierre. Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
    • Weller, Michael. Department of Neurology, University of Tübingen, Tübingen, Germany
    • van den Bent, Martin. Department of Neurology, Erasmus Medical Center, Rotterdam, The Netherlands
    • Mason, Warren. Princess Margaret Hospital, University of Toronto, Toronto, Canada
    • Mirimanoff, René-Olivier. Department of Radio-Oncology, Lausanne University Hospital, Lausanne, Switzerland
    • Stupp, Roger. Department of Clinical Neurosciences, Lausanne University Hospital, Lausanne, Switzerland
    • Mokhtari, Karima. Laboratoire de Neuropathologie R. Escourolle, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
    • Wesseling, Pieter. Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
    Type de document
    • Postprint
    Identifiant OAI-PMH
    • oai:doc.rero.ch:313984
    Summary
    Glioblastoma (GBM) is a morphologically heterogeneous tumor type with a median survival of only 15months 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