title: Changes in the EGFR amplification and EGFRvIII expression between paired primary and recurrent glioblastomas.
abstract: BACKGROUND
  The efficacy of novel targeted therapies is often tested at the time of tumor recurrence. However, for glioblastoma (GBM) patients, surgical resections at recurrence are performed only in a minority of patients; therefore, molecular data are predominantly derived from the initial tumor. Molecular data of the initial tumor for patient selection into personalized medicine trials can therefore be used only when the specific genetic change is retained in the recurrent tumor.
  
  
  METHODS
  In this study we determined whether EGFR amplification and expression of the most common mutation in GBMs (EGFRvIII) is retained at tumor recurrence. Because retention of genetic changes may be dependent on the initial treatment, we only used a cohort of GBM samples that were uniformly treated according to the current standard of care (ie, chemo-irradiation with temozolomide).
  
  
  RESULTS
  Our data show that, in spite of some quantitative differences, the EGFR amplification status remains stable in the majority (84%) of tumors evaluated. EGFRvIII expression remained similar in 79% of GBMs. However, within the tumors expressing EGFRvIII at initial diagnosis, approximately one-half lose their EGFRvIII expression at tumor recurrence.
  
  
  CONCLUSIONS
  The relative stability of EGFR amplification indicates that molecular data obtained in the primary tumor can be used to predict the EGFR status of the recurrent tumor, but care should be taken in extrapolating EGFRvIII expression from the primary tumor, particularly when expressed at first diagnosis.
authors.affiliation: Department of Neurology, Erasmus MC, Rotterdam, Netherlands (M.J.v.d.B., Y.G., K.v.Z., J.P., P.A.S.S., P.J.F.); Department of Pathology, Erasmus MC, Rotterdam, Netherlands (J.M.K.); Department of Neurology, Haaglanden MC, The Hague, Netherlands (M.K., M.T.); EORTC Headquarters, Brussels, Belgium (T.G.); Pathology Department, Leiden University Medical Center, Leiden, Netherlands (S.v.D.).
authors.forename: Martin J
authors.initials: MJ
authors.lastname: van den Bent
authors.affiliation: Department of Neurology, Erasmus MC, Rotterdam, Netherlands (M.J.v.d.B., Y.G., K.v.Z., J.P., P.A.S.S., P.J.F.); Department of Pathology, Erasmus MC, Rotterdam, Netherlands (J.M.K.); Department of Neurology, Haaglanden MC, The Hague, Netherlands (M.K., M.T.); EORTC Headquarters, Brussels, Belgium (T.G.); Pathology Department, Leiden University Medical Center, Leiden, Netherlands (S.v.D.).
authors.forename: Ya
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Neurology, Erasmus MC, Rotterdam, Netherlands (M.J.v.d.B., Y.G., K.v.Z., J.P., P.A.S.S., P.J.F.); Department of Pathology, Erasmus MC, Rotterdam, Netherlands (J.M.K.); Department of Neurology, Haaglanden MC, The Hague, Netherlands (M.K., M.T.); EORTC Headquarters, Brussels, Belgium (T.G.); Pathology Department, Leiden University Medical Center, Leiden, Netherlands (S.v.D.).
authors.forename: Melissa
authors.initials: M
authors.lastname: Kerkhof
authors.affiliation: Department of Neurology, Erasmus MC, Rotterdam, Netherlands (M.J.v.d.B., Y.G., K.v.Z., J.P., P.A.S.S., P.J.F.); Department of Pathology, Erasmus MC, Rotterdam, Netherlands (J.M.K.); Department of Neurology, Haaglanden MC, The Hague, Netherlands (M.K., M.T.); EORTC Headquarters, Brussels, Belgium (T.G.); Pathology Department, Leiden University Medical Center, Leiden, Netherlands (S.v.D.).
authors.forename: Johan M
authors.initials: JM
authors.lastname: Kros
authors.affiliation: Department of Neurology, Erasmus MC, Rotterdam, Netherlands (M.J.v.d.B., Y.G., K.v.Z., J.P., P.A.S.S., P.J.F.); Department of Pathology, Erasmus MC, Rotterdam, Netherlands (J.M.K.); Department of Neurology, Haaglanden MC, The Hague, Netherlands (M.K., M.T.); EORTC Headquarters, Brussels, Belgium (T.G.); Pathology Department, Leiden University Medical Center, Leiden, Netherlands (S.v.D.).
authors.forename: Thierry
authors.initials: T
authors.lastname: Gorlia
authors.affiliation: Department of Neurology, Erasmus MC, Rotterdam, Netherlands (M.J.v.d.B., Y.G., K.v.Z., J.P., P.A.S.S., P.J.F.); Department of Pathology, Erasmus MC, Rotterdam, Netherlands (J.M.K.); Department of Neurology, Haaglanden MC, The Hague, Netherlands (M.K., M.T.); EORTC Headquarters, Brussels, Belgium (T.G.); Pathology Department, Leiden University Medical Center, Leiden, Netherlands (S.v.D.).
authors.forename: Kitty
authors.initials: K
authors.lastname: van Zwieten
authors.affiliation: Department of Neurology, Erasmus MC, Rotterdam, Netherlands (M.J.v.d.B., Y.G., K.v.Z., J.P., P.A.S.S., P.J.F.); Department of Pathology, Erasmus MC, Rotterdam, Netherlands (J.M.K.); Department of Neurology, Haaglanden MC, The Hague, Netherlands (M.K., M.T.); EORTC Headquarters, Brussels, Belgium (T.G.); Pathology Department, Leiden University Medical Center, Leiden, Netherlands (S.v.D.).
authors.forename: Jory
authors.initials: J
authors.lastname: Prince
authors.affiliation: Department of Neurology, Erasmus MC, Rotterdam, Netherlands (M.J.v.d.B., Y.G., K.v.Z., J.P., P.A.S.S., P.J.F.); Department of Pathology, Erasmus MC, Rotterdam, Netherlands (J.M.K.); Department of Neurology, Haaglanden MC, The Hague, Netherlands (M.K., M.T.); EORTC Headquarters, Brussels, Belgium (T.G.); Pathology Department, Leiden University Medical Center, Leiden, Netherlands (S.v.D.).
authors.forename: Sjoerd
authors.initials: S
authors.lastname: van Duinen
authors.affiliation: Department of Neurology, Erasmus MC, Rotterdam, Netherlands (M.J.v.d.B., Y.G., K.v.Z., J.P., P.A.S.S., P.J.F.); Department of Pathology, Erasmus MC, Rotterdam, Netherlands (J.M.K.); Department of Neurology, Haaglanden MC, The Hague, Netherlands (M.K., M.T.); EORTC Headquarters, Brussels, Belgium (T.G.); Pathology Department, Leiden University Medical Center, Leiden, Netherlands (S.v.D.).
authors.forename: Peter A
authors.initials: PA
authors.lastname: Sillevis Smitt
authors.affiliation: Department of Neurology, Erasmus MC, Rotterdam, Netherlands (M.J.v.d.B., Y.G., K.v.Z., J.P., P.A.S.S., P.J.F.); Department of Pathology, Erasmus MC, Rotterdam, Netherlands (J.M.K.); Department of Neurology, Haaglanden MC, The Hague, Netherlands (M.K., M.T.); EORTC Headquarters, Brussels, Belgium (T.G.); Pathology Department, Leiden University Medical Center, Leiden, Netherlands (S.v.D.).
authors.forename: Martin
authors.initials: M
authors.lastname: Taphoorn
authors.affiliation: Department of Neurology, Erasmus MC, Rotterdam, Netherlands (M.J.v.d.B., Y.G., K.v.Z., J.P., P.A.S.S., P.J.F.); Department of Pathology, Erasmus MC, Rotterdam, Netherlands (J.M.K.); Department of Neurology, Haaglanden MC, The Hague, Netherlands (M.K., M.T.); EORTC Headquarters, Brussels, Belgium (T.G.); Pathology Department, Leiden University Medical Center, Leiden, Netherlands (S.v.D.).
authors.forename: Pim J
authors.initials: PJ
authors.lastname: French
mesh_terms: D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism; D066246:ErbB Receptors / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005784:Gene Amplification; D005909:Glioblastoma / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000378:metabolism*
chemical_list: C410723:epidermal growth factor receptor VIII; C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: EGFR; EGFRvIII; glioblastoma; recurrent tumors