title: Epidermal growth factor receptor: is it a feasible target for the treatment of osteosarcoma?
abstract: OBJECTIVE
  Features of epidermal growth factor receptor (EGFR) expression in osteosarcoma and in vitro efficacies of EGFR inhibitors against osteosarcoma cells were evaluated.
  
  
  METHODS
  Thirty biopsy samples of osteosarcoma patients were retrospectively analyzed for EGFR protein expression by immunohistochemistry. Relationships between EGFR expression and clinicopathologic characteristics and treatment outcomes were evaluated. Four osteosarcoma cell lines were analyzed for EGFR and p-EGFR expression by western blotting. Efficacies of gefitinib and BIBW2992 on osteosarcoma cells were evaluated using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Tyrosine kinase domains in exons 18 to 21 were sequenced and gene expression analyses of EGFR and PTEN were performed in four osteosarcoma cell lines.
  
  
  RESULTS
  EGFR protein was expressed in 27 (90%) samples (6 low, 12 intermediate, 9 high) and in three cell lines. Intermediate or high staining for EGFR was related to a tumor volume<150 mL (p<0.001) and histologic subtype other than osteoblastic type (p=0.03). However, EGFR expression was not associated with histologic response to preoperative chemotherapy or survival. Gefitinib and BIBW 2992 did not have any significant inhibitory effect on cell viabilities. DNA sequencing analysis revealed three osteosarcoma cell lines have single base changes at codon 2361 of exon 20 (G to A), without affecting translation results. Furthermore, no mutation was found to be associated with constitutive EGFR activation.
  
  
  CONCLUSIONS
  In the present study, gefitinib and BIBW2992 were not effective against osteosarcoma cells. However, as osteosarcoma cells express EGFR, further studies are necessary to explore the potential of other therapeutic agents targeting EGFR.
authors.affiliation: Department of Pediatrics, Korea Cancer Center Hospital, Seoul, Korea.
authors.forename: Jun Ah
authors.initials: JA
authors.lastname: Lee
authors.forename: Yunmi
authors.initials: Y
authors.lastname: Ko
authors.forename: Dong Ho
authors.initials: DH
authors.lastname: Kim
authors.forename: Jung Sub
authors.initials: JS
authors.lastname: Lim
authors.forename: Chang-Bae
authors.initials: CB
authors.lastname: Kong
authors.forename: Wan Hyeong
authors.initials: WH
authors.lastname: Cho
authors.forename: Dae-Geun
authors.initials: DG
authors.lastname: Jeon
authors.forename: Soo-Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: Jae-Soo
authors.initials: JS
authors.lastname: Koh
keywords: Epidermal growth factor receptor; Osteosarcoma; Treatment