title: Epidermal growth factor receptor overexpression is common and not correlated to gene copy number in ependymoma.
abstract: OBJECTIVE
  The aim of this study was to investigate the epidermal growth factor receptor (EGFR) status in ependymoma specimens, as there is a need for new prognostic and druggable targets in this disease.
  
  
  METHODS
  Ependymomas (WHO grade II, n = 40; WHO grade III, n = 15) located spinal (n = 35), infratentorial (n = 14), and supratentorial (n = 6) of 53 patients with a median age of 40 (range, 2-79) years were analyzed for Ki-67, p53, and EGFR expression by immunohistochemistry using a tissue microarray and for EGFR gene copy number alterations/mutations. Results were correlated to clinical data.
  
  
  RESULTS
  EGFR overexpression was found in 30/60% of ependymomas depending on the antibody used and was more pronounced in WHO grade III. High EGFR gene copy number gains were found in 6 (11%) ependymomas with half of them being amplifications. EGFR amplified ependymomas displayed an EGFR overexpression with both antibodies in two of three cases. A missense mutation in exon 20 of EGFR (S768I) was detected in one amplified case.
  
  
  CONCLUSIONS
  EGFR is frequently overexpressed in ependymomas. Other mechanisms than amplification of the EGFR gene appear to contribute to EGFR overexpression in most cases. EGFR mutations may be present in a small subset of ependymomas.
authors.affiliation: Division of Pediatric Oncology, Hematology and Hemostaseology, Department of Woman's and Children's Health, University Hospital Leipzig, Leipzig, Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Friedrich
authors.affiliation: Department of Pediatric Hematology and Oncology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.|Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University Medical Center Goettingen, Goettingen, Germany.|Department of Pediatrics and Adolescent Medicine, Division of Pediatric Hematology and Oncology, University Hospital of Geneva, Geneva, Switzerland.
authors.forename: André O
authors.initials: AO
authors.lastname: von Bueren
authors.affiliation: Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany.
authors.forename: Larissa
authors.initials: L
authors.lastname: Kolevatova
authors.affiliation: Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bernreuther
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Grob
authors.affiliation: Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany.
authors.forename: Diego
authors.initials: D
authors.lastname: Sepulveda-Falla
authors.affiliation: Department of Neurological Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Leander
authors.initials: L
authors.lastname: van den Boom
authors.affiliation: Department of Neurological Surgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Manfred
authors.initials: M
authors.lastname: Westphal
authors.affiliation: Institute of Pathology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Ronald
authors.initials: R
authors.lastname: Simon
authors.affiliation: Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, D-20246, Hamburg, Germany. m.glatzel@uke.de.
authors.forename: Markus
authors.initials: M
authors.lastname: Glatzel
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D004806:Ependymoma / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D018628:Gene Dosage / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D015192:Infratentorial Neoplasms / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D013120:Spinal Cord Neoplasms / Q000235:genetics*; D015173:Supratentorial Neoplasms / Q000235:genetics; D046888:Tissue Array Analysis; D055815:Young Adult
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: Brain tumor; Diagnosis; Ependymoma; Epidermal growth factor receptor; Gene amplification; Targeted therapy