title: The natural history of EGFR and EGFRvIII in glioblastoma patients.
abstract: BACKGROUND
  The epidermal growth factor receptor (EGFR) is over expressed in approximately 50-60% of glioblastoma (GBM) tumors, and the most common EGFR mutant, EGFRvIII, is expressed in 24-67% of cases. This study was designed to address whether over expressed EGFR or EGFRvIII is an actual independent prognostic indicator of overall survival in a uniform body of patients in whom gross total surgical resection (GTR; > or = 95% resection) was not attempted or achieved.
  
  
  METHODS
  Biopsed or partially/subtotally resected GBM patients (N = 54) underwent adjuvant conformal radiation and chemotherapy. Their EGFR and EGFRvIII status was determined by immunohistochemistry and Kaplan-Meier estimates of overall survival were obtained.
  
  
  RESULTS
  In our study of GBM patients with less than GTR, 42.6% (n = 23) failed to express EGFR, 25.9% (n = 14) had over expression of the wild-type EGFR only and 31.5 % (n = 17) expressed the EGFRvIII. Patients within groups expressing the EGFR, EGFRvIII, or lacking EGFR expression did not differ in age, Karnofsky Performance Scale (KPS) score, extent of tumor resection. They all had received postoperative radiation and chemotherapy. The median overall survival times for patients with tumors having no EGFR expression, over expressed EGFR only, or EGFRvIII were 12.3 (95% CI, 8.04-16.56), 11.03 (95% CI, 10.18-11.89) and 14.07 (95% CI, 7.39-20.74) months, respectively, log rank test p > 0.05). Patients with tumors that over expressed the EGFR and EGFRvIII were more likely to present with ependymal spread, 21.4% and 35.3% respectively, compared to those patients whose GBM failed to express either marker, 13.0%, although the difference was not statistically significant. There was no significant difference in multifocal disease or gliomatosis cerebri among EGFR expression groups.
  
  
  CONCLUSIONS
  The over expressed wild-type EGFR and EGFRvIII are not independent predictors of median overall survival in the cohort of patients who did not undergo extensive tumor resection.
authors.affiliation: Department of Neurosurgery, The Brain Tumor Center, The University of Texas M, D, Anderson Cancer Center, Houston, Texas, USA. aheimber@mdanderson.org
authors.forename: Amy B
authors.initials: AB
authors.lastname: Heimberger
authors.forename: Dima
authors.initials: D
authors.lastname: Suki
authors.forename: David
authors.initials: D
authors.lastname: Yang
authors.forename: Weiming
authors.initials: W
authors.lastname: Shi
authors.forename: Kenneth
authors.initials: K
authors.lastname: Aldape