title: Activation of EGFR signaling from pilocytic astrocytomas to glioblastomas.
abstract: BACKGROUND
  EGFR analyses allow for better correlation between genotype and phenotype in astrocytomas and represent an attractive therapeutic target. Most studies emphasize analyses of EGFR in glioblastomas (GBMs) but do not analyze all grades of astrocytomas (from pilocytic to GBM). The purpose of our study was to evaluate the status of EGFR (expression, deletion, and amplification) and EGFR protein expression in all grades of astrocytomas.
  
  
  METHODS
  We analyzed a total of 145 surgical tumor specimens that included: 22 pilocytic astrocytomas, 22 grade II astrocytomas, 17 grade III astrocytomas and 84 GBMs. The specimens were compared to 17 non-neoplastic brain tissues obtained from epilepsy surgery. EGFR expression, EGFR amplification and EGFRvIII analyses were performed by quantitative real-time PCR, and protein expression was evaluated by immunohistochemistry.
  
  
  RESULTS
  EGFR relative overexpression and EGFR amplification were observed, respectively, in 50% and 20% of astrocytomas, while EGFRvIII was only found in GBMs (34.5%, p=0.005). Amongst EGFR-amplified GBM cases, 59% also presented EGFRvIII (p<0.001). Cytoplasmic accumulation of EGFR protein was detected in 75% of astrocytomas, and 21% of the astrocytomas showed nuclear localization (p=0.003).
  
  
  CONCLUSIONS
  EGFR alterations were found in all grades of astrocytomas, from pilocytic to GBMs, while EGFRvIII was exclusively found in GBMs. These findings provide important information on the mechanisms involved in the progression of astrocytomas for determining whether EGFR status can be used for effective and specific therapy.
authors.affiliation: Department of Neurology, School of Medicine, University of São Paulo - Brazil.
authors.forename: Priscila O
authors.initials: PO
authors.lastname: Carvalho
authors.forename: Miyuki
authors.initials: M
authors.lastname: Uno
authors.forename: Sueli M
authors.initials: SM
authors.lastname: Oba-Shinjo
authors.forename: Sergio
authors.initials: S
authors.lastname: Rosemberg
authors.forename: Alda
authors.initials: A
authors.lastname: Wakamatsu
authors.forename: Clemar C
authors.initials: CC
authors.lastname: da Silva
authors.forename: Manoel J
authors.initials: MJ
authors.lastname: Teixeira
authors.forename: Suely K N
authors.initials: SK
authors.lastname: Marie
mesh_terms: D000328:Adult; D001254:Astrocytoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D001932:Brain Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D066246:ErbB Receptors / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000628:therapy; D006801:Humans; D008297:Male; D015398:Signal Transduction; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors