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

Abstract

<b>Purpose:</b> Approximately 40% of all glioblastomas have amplified the <i>EGFR</i> gene, and about half of these tumors express the EGFRvIII variant. The prognostic role of EGFRvIII in <i>EGFR</i>-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.<b>Experimental Design:</b><i>EGFR</i>-amplified glioblastomas from 106 patients were assessed for EGFRvIII positivity. Changes in <i>EGFR</i> amplification and EGFRvIII status from primary to recurrent glioblastomas were evaluated in 40 patients with <i>EGFR</i>-amplified tumors and 33 patients with <i>EGFR</i>-nonamplified tumors. <i>EGFR</i> 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.<b>Results:</b> Sixty of 106 <i>EGFR</i>-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 <i>EGFR</i>-amplified primary tumors (87.5%). Four patients lost and one patient gained EGFRvIII positivity at recurrence. None of 33 <i>EGFR-</i>nonamplified glioblastomas acquired <i>EGFR</i> amplification or EGFRvIII at recurrence. <i>EGFR</i> SNVs were frequent in <i>EGFR</i>-amplified tumors, but were not linked to survival.<b>Conclusions:</b> EGFRvIII and <i>EGFR</i> SNVs are not prognostic in <i>EGFR</i>-amplified glioblastoma patients. <i>EGFR</i> 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. <i>Clin Cancer Res; 23(22); 6846-55. ©2017 AACR</i>.