title: Genomic amplification and high expression of EGFR are key targetable oncogenic events in malignant peripheral nerve sheath tumor.
abstract: BACKGROUND
  The dismal outcome of malignant peripheral nerve sheath tumor (MPNST) highlights the necessity of finding new therapeutic methods to benefit patients with this aggressive sarcoma. Our purpose was to investigate epidermal growth factor receptor (EGFR) as a potential therapeutic target in MPNSTs.
  
  
  METHODS
  We performed a microarray based-comparative genomic hybridization (aCGH) profiling of two cohorts of primary MPNST tissue samples including 25 patients treated at The University of Texas MD Anderson Cancer Center (MD Anderson) and 26 patients from Tianjin Medical University Cancer Institute & Hospital (TMUCIH). Fluorescence in situ hybridization (FISH) method was used to validate the gene amplification detected by aCGH analysis. Another independent cohort of 56 formalin fixed paraffin embedded (FFPE) MPNST samples was obtained to explore EGFR protein expression by immunohistochemical analysis. Cell biology detection and validation were performed on human MPNST cell lines ST88-14 and STS26T.
  
  
  RESULTS
  aCGH and pathway analysis of the 51 MPNSTs identified significant gene amplification events in EGFR pathway, including frequent amplifications of EGFR gene itself, which was subsequently validated by FISH assay. High expression of EGFR protein was associated with poor disease-free and overall survival of human MPNST patients. In human MPNST cell lines ST88-14 and STS26T, inhibition of EGFR by siRNA or Gefitinib led to decreased cell proliferation, migration, and invasion accompanied by attenuation of PI3K/AKT and MAPK pathways.
  
  
  CONCLUSIONS
  These results suggest that EGFR is a potential therapeutic target for MPNST.
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Du
authors.affiliation: Department of Bone and Soft Tissue Tumor, National Clinical Cancer Research Center, Tianjin Medical University Cancer Institute & Hospital, Tianjin 300060, China. yangjilong@tjmuch.com.
authors.forename: Jilong
authors.initials: J
authors.lastname: Yang
authors.forename: Antti
authors.initials: A
authors.lastname: Ylipää
authors.forename: Ze
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D055028:Comparative Genomic Hybridization; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D018317:Nerve Sheath Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016019:Survival Analysis
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors