Expression of EGFRvIII in glioblastoma: Prognostic significance revisited

Nicola Montano, Tonia Cenci, Maurizio Martini, Quintino Giorgio D'Alessandris, Federica Pelacchi, Lucia Ricci-Vitiani, Giulio Maira, Ruggero de Maria, Luigi Maria Larocca, Roberto Pallini

Research output: Contribution to journalArticle

Abstract

The epidermal growth factor receptor variant III (EGFRvIII) is associated with increased proliferation of glioma cells. However, the impact of EGFRvIII on survival of patients with glioblastoma (GBM) has not been definitively established. In the present study, we prospectively evaluated 73 patients with primary GBM treated with surgical resection and standard radio/chemotherapy. The EGFRvIII was assessed by reverse transcription-polymerase chain reaction (PCR), O6-methylguanine methyltransferase (MGMT) promoter methylation was assessed by methylationspecific PCR, and phosphatase and tension homolog (PTEN) expression was assessed by immunohistochemistry. In 14 patients of this series, who presented with tumor recurrence, EGFRvIII was determined by real-time PCR. Sensitivity to temozolomide (TMZ) was assessed in vitro on GBM neurosphere cell cultures with different patterns of EGFRvIII expression. Age 60 years or younger, preoperative Karnofsky Performance Status score of 70 or higher, recursive partitioning analysis score III and IV, methylated MGMT, and Ki67 index of 20% or less were significantly associated with longer overall survival (OS; P =.0069, P =.0035, P =.0007, P =.0437, and P =.0286, respectively). EGFRvIII identified patients with significantly longer OS (P =.0023) and the association of EGFRvIII/Ki67 of 20% or less, EGFRvIII/normal PTEN, EGFRvIII/methylated MGMT, and EGFRvIII/normal PTEN/methylated MGMT identified subgroups of GBM patients with better prognosis. In recurred GBMs, EGFRvIII expression was approximately twofold lower than in primary tumors. In vitro, the EGFRvIII-negative GBM neurosphere cells were more resistant to TMZ than the positive ones. In conclusion, in contrast with previous studies, we found that EGFRvIII is associated with prolonged survival of GBM patients treated with surgery and radio/chemotherapy. Depletion of EGFRvIII in recurrent GBMs as well as differential sensitivity to TMZ in vitro indicates that the EGFRvIII-negative cell fraction is involved in resistance to radio/chemotherapy and tumor repopulation.

Original languageEnglish
Pages (from-to)1113-1121
Number of pages9
JournalNeoplasia (United States)
Volume13
Issue number12
DOIs
Publication statusPublished - Dec 2011

ASJC Scopus subject areas

  • Cancer Research

Fingerprint Dive into the research topics of 'Expression of EGFRvIII in glioblastoma: Prognostic significance revisited'. Together they form a unique fingerprint.

  • Cite this

    Montano, N., Cenci, T., Martini, M., D'Alessandris, Q. G., Pelacchi, F., Ricci-Vitiani, L., Maira, G., de Maria, R., Larocca, L. M., & Pallini, R. (2011). Expression of EGFRvIII in glioblastoma: Prognostic significance revisited. Neoplasia (United States), 13(12), 1113-1121. https://doi.org/10.1593/neo.111338