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

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

*Corresponding author for this work

Research output: Contribution to journalReview article

63 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)841-852
Number of pages12
JournalActa Neuropathologica
Volume123
Issue number6
DOIs
StatePublished - Jun 1 2012

    Fingerprint

Keywords

  • EGFR
  • Glioblastoma
  • Glioblastoma with oligodendroglioma-like component
  • IDH1
  • MGMT
  • Pathology
  • Prognostic factors
  • Pseudopalisading necrosis
  • Randomized trial
  • Temozolomide

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

Hegi, M. E., Janzer, R. C., Lambiv, W. L., Gorlia, T., Kouwenhoven, M. C. M., Hartmann, C., Von Deimling, A., Martinet, D., Schmutz, N. B., 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. (2012). 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. Acta Neuropathologica, 123(6), 841-852. https://doi.org/10.1007/s00401-011-0938-4