Epidermal growth factor receptor overexpression is common and not correlated to gene copy number in ependymoma

Childs Nerv Syst. 2016 Feb;32(2):281-90. doi: 10.1007/s00381-015-2981-2. Epub 2015 Dec 21.

Abstract

Purpose: 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.

Keywords: Brain tumor; Diagnosis; Ependymoma; Epidermal growth factor receptor; Gene amplification; Targeted therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Brain Neoplasms / genetics*
  • Child
  • Child, Preschool
  • Ependymoma / genetics*
  • ErbB Receptors / genetics*
  • Female
  • Gene Dosage / genetics*
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization, Fluorescence
  • Infratentorial Neoplasms / genetics
  • Male
  • Middle Aged
  • Mutation
  • Spinal Cord Neoplasms / genetics*
  • Supratentorial Neoplasms / genetics
  • Tissue Array Analysis
  • Young Adult

Substances

  • EGFR protein, human
  • ErbB Receptors