title: Immunohistochemically determined total epidermal growth factor receptor levels not of prognostic value in newly diagnosed glioblastoma multiforme: report from the Radiation Therapy Oncology Group.
abstract: OBJECTIVE
  The Radiation Therapy Oncology Group (RTOG) performed an analysis of patterns of immunohistochemically detected total epidermal growth factor receptor (EGFR) protein expression levels and their prognostic significance on archival tissue in newly diagnosed glioblastoma multiforme (GBM) patients from prior prospective RTOG clinical trials.
  
  
  METHODS
  Patients in this study had been treated on previous RTOG GBM trials (RTOG 7401, 7918, 8302, 8409, 9006, 9305, 9602, and 9806). Tissue microarrays were prepared from 155 patients enrolled in these trials. These specimens were stained using a mouse monoclonal antibody specific for the extracellular binding domain of EGFR to detect total EGFR (including both wild-type phosphorylated and wild-type unphosphorylated isoforms with some cross-reactivity with EGFRvIII). The intensity of total EGFR protein expression was measured by computerized quantitative image analysis using the SAMBA 4000 Cell Image Analysis System. The parameters measured were the mean optical densities over the labeled areas and the staining index, which represents the proportion of stained area relative to the mean stain concentration. Both parameters were correlated with the clinical outcome.
  
  
  RESULTS
  No differences in either overall or progression-free survival could be demonstrated by the mean optical density class or mean optical density quartile or the staining index of total EGFR immunostaining among the representative RTOG GBM cases.
  
  
  CONCLUSIONS
  Total EGFR protein expression levels, as measured immunohistochemically, do not appear to be of prognostic value in newly diagnosed GBM patients. Given the accumulating clinical evidence of the activity of anti-EGFR agents in GBM and the preclinical data suggesting the important role of downstream mediators as effectors of EGFR signaling, the RTOG is conducting additional investigations into the prognostic value of activation patterns of EGFR signaling, both at the level of the receptor (e.g., EGFRvIII, phospho-EGFR) and at the level of downstream signal transduction pathways (e.g., PI3K, Ras/MAPK pathways).
authors.affiliation: Department of Radiation Oncology, Massachusetts General Hospital/Harvard Medical School, Boston, MA 02114, USA. achakravarti@partners.org
authors.forename: Arnab
authors.initials: A
authors.lastname: Chakravarti
authors.forename: Wendy
authors.initials: W
authors.lastname: Seiferheld
authors.forename: Xiaoyu
authors.initials: X
authors.lastname: Tu
authors.forename: Huijun
authors.initials: H
authors.lastname: Wang
authors.forename: Hua Zhong
authors.initials: HZ
authors.lastname: Zhang
authors.forename: K Kian
authors.initials: KK
authors.lastname: Ang
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Hammond
authors.forename: Walter
authors.initials: W
authors.lastname: Curran
authors.forename: Minesh
authors.initials: M
authors.lastname: Mehta
mesh_terms: D001932:Brain Neoplasms / Q000737:chemistry* / Q000532:radiotherapy; D066246:ErbB Receptors / Q000032:analysis*; D005260:Female; D005909:Glioblastoma / Q000737:chemistry* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000032:analysis*; D011379:Prognosis
chemical_list: D009363:Neoplasm Proteins; D066246:ErbB Receptors