The
epidermal growth factor receptor vIII mutant (
EGFRvIII) is found in ~50% of all EGFR-amplified
glioblastomas and constitutes a
tumor-specific therapeutic target. To assess molecular testing approaches and the prognostic role of
EGFRvIII in patients treated according to current standards of care, we compared different
EGFRvIII detection methods and correlated
EGFRvIII status with outcome in a prospective patient cohort of the German
Glioma Network. In total, 184 newly diagnosed
glioblastoma patients were investigated for EGFR amplification and for expression of EGFR and
EGFRvIII by immunohistochemistry. Further, the
EGFRvIII status was additionally studied by multiplex
ligation-dependent probe amplification (MLPA) analysis and reverse transcription-PCR (RT-PCR). Immunohistochemistry demonstrated
EGFRvIII in 34 of 184 patients (18%). RT-PCR or MLPA analysis detected four additional
EGFRvIII-positive patients. Overall, RT-PCR and immunohistochemistry were more sensitive for
EGFRvIII detection than MLPA.
EGFRvIII status was not associated with progression-free and overall survival.
EGFRvIII also had no prognostic significance in the subgroup of patients who were free from progression after
concomitant radiochemotherapy and thus would be eligible for the ongoing ACT IV
EGFRvIII vaccination trial. Age, extent of resection and O⁶-methylguanine
DNA methyltransferase (MGMT) promoter methylation status appeared to be less prognostic in
EGFRvIII-positive patients. Thus,
EGFRvIII positivity is not a major negative prognostic factor in
glioblastoma patients treated according to current standards of care. Data from phase II
EGFRvIII-targeted vaccination trials compare favorably with the present contemporary results, supporting the further exploration of EGVRvIII vaccination in newly diagnosed
glioblastoma.