Presence of an oligodendroglioma-like component in newly diagnosed glioblastoma identifies a pathogenetically heterogeneous subgroup and lacks prognostic value

• Verfasst von: Hegi, Monika E. [VerfasserIn]
• Verfasst von: Hartmann, Christian [VerfasserIn]
• Verfasst von: Deimling, Andreas von [VerfasserIn]
• Titel: Presence of an oligodendroglioma-like component in newly diagnosed glioblastoma identifies a pathogenetically heterogeneous subgroup and lacks prognostic value
• Titelzusatz: central pathology review of the EORTC_26981/NCIC_CE.3 trial
• Verf.angabe: 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
• E-Jahr: 2012
• Jahr: 15 January 2012
• Umfang: 12 S.
• Fussnoten: Gesehen am 06.04.2018
• Titel Quelle: Enthalten in: Acta neuropathologica
• Ort Quelle: Berlin : Springer, 1961
• Jahr Quelle: 2012
• Band/Heft Quelle: 123(2012), 6, Seite 841-852
• ISSN Quelle: 1432-0533
• DOI: doi:10.1007/s00401-011-0938-4
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1571784381

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.