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 language | English (US) |
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Pages (from-to) | 841-852 |
Number of pages | 12 |
Journal | Acta Neuropathologica |
Volume | 123 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2012 |
Funding
Acknowledgments We thank all the patients who participated in the study and provided informed consent for translational research on their tumor tissues. We acknowledge the great contributions of the local pathologists, and the physicians and nurses taking care of the patients. We thank Solange Gros and Sylviane Trepey for their excellent technical support. Translational research in this study was supported by the Swiss National Science Foundation 3100A0_122557/1 (MEH), the Amadéo and Nélia Barletta Foundation (MEH, RS), the Jacqueline Seroussi Foundation (MEH) and the EORTC (TRF/04/01, TRF/02/03). Additional support was given by grants from the National Cancer Institute (5U10 CA11488-30 through 2U10 CA011488-41; Bethesda, Maryland, USA) and by the EORTC Charitable Trust. The content of this manuscript is solely the responsibility of the authors and does not necessarily reflect the official views of the National Cancer Institute.
Keywords
- EGFR
- Glioblastoma
- Glioblastoma with oligodendroglioma-like component
- IDH1
- MGMT
- Pathology
- Prognostic factors
- Pseudopalisading necrosis
- Randomized trial
- Temozolomide
ASJC Scopus subject areas
- Clinical Neurology
- Cellular and Molecular Neuroscience
- Pathology and Forensic Medicine