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Clin Cancer Res. 2017 Nov 15;23(22):6846-6855. doi: 10.1158/1078-0432.CCR-17-0890. Epub 2017 Aug 29.

Epidermal Growth Factor Receptor Variant III (EGFRvIII) Positivity in EGFR-Amplified Glioblastomas: Prognostic Role and Comparison between Primary and Recurrent Tumors.

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Department of Neuropathology, Heinrich Heine University Hospital, Düsseldorf, Germany.
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany.
Department of Neuropathology, Heinrich Heine University Hospital, Düsseldorf, Germany.
Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
Department of Neurosurgery, Heinrich Heine University, Düsseldorf, Germany.
Department of Neurosurgery, University of Bonn, Bonn, Germany.
Department of Neurosurgery, University of Hamburg, Hamburg, Germany.
Department of Neurosurgery, University of Dresden, Dresden, Germany.
Department of Neurosurgery, University of Munich (LMU), Munich, Germany.
German Cancer Consortium (DKTK), partner site Munich (LMU), Munich, Germany.
Department of Neuropathology, University of Bonn, Bonn, Germany.
University Hospital of Heidelberg, Institute for Pathology, Department of Neuropathology, and German Cancer Research Center (DKFZ), Clinical Cooperation Unit Neuropathology, Heidelberg, Germany.
German Cancer Consortium (DKTK), partner site Essen/Düsseldorf, Germany.


Purpose: Approximately 40% of all glioblastomas have amplified the EGFR gene, and about half of these tumors express the EGFRvIII variant. The prognostic role of EGFRvIII in EGFR-amplified glioblastoma patients and changes in EGFRvIII expression in recurrent versus primary glioblastomas remain controversial, but such data are highly relevant for EGFRvIII-targeted therapies.Experimental Design:EGFR-amplified glioblastomas from 106 patients were assessed for EGFRvIII positivity. Changes in EGFR amplification and EGFRvIII status from primary to recurrent glioblastomas were evaluated in 40 patients with EGFR-amplified tumors and 33 patients with EGFR-nonamplified tumors. EGFR single-nucleotide variants (SNV) were assessed in 27 patients. Data were correlated with outcome and validated in 150 glioblastoma patients from The Cancer Genome Atlas (TCGA) consortium.Results: Sixty of 106 EGFR-amplified glioblastomas were EGFRvIII-positive (56.6%). EGFRvIII positivity was not associated with different progression-free or overall survival. EGFRvIII status was unchanged at recurrence in 35 of 40 patients with EGFR-amplified primary tumors (87.5%). Four patients lost and one patient gained EGFRvIII positivity at recurrence. None of 33 EGFR-nonamplified glioblastomas acquired EGFR amplification or EGFRvIII at recurrence. EGFR SNVs were frequent in EGFR-amplified tumors, but were not linked to survival.Conclusions: EGFRvIII and EGFR SNVs are not prognostic in EGFR-amplified glioblastoma patients. EGFR amplification is retained in recurrent glioblastomas. Most EGFRvIII-positive glioblastomas maintain EGFRvIII positivity at recurrence. However, EGFRvIII expression may change in a subset of patients at recurrence, thus repeated biopsy with reassessment of EGFRvIII status is recommended for patients with recurrent glioblastoma to receive EGFRvIII-targeting agents. Clin Cancer Res; 23(22); 6846-55. ©2017 AACR.

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