title: Epidermal growth factor receptor expression in high-grade osteosarcomas is associated with a good clinical outcome.
abstract: OBJECTIVE
  The expression of the epidermal growth factor receptor (EGFR) in osteosarcomas has repeatedly been described. With the introduction of anti-EGFR-targeted therapies in clinical practice, these findings regain increased attention. Experience with anti-EGFR-targeted therapies in other cancers has made clear that besides the expression status of EGFR, a detailed knowledge about gene mutations is of major predictive power. We therefore aimed to explore the EGFR expression and gene mutation status in high-grade osteosarcomas.
  
  
  METHODS
  We investigated tumor samples of osteosarcoma patients of all age groups by means of immunohistochemistry (n=111) and egfr fluorescence in situ hybridization (n=39). Sixty-three patients were treated according to the Cooperative Osteosarcoma Study Group protocols and complete clinical follow-up was available in these cases.
  
  
  RESULTS
  Ninety-one of 111 (81%) of osteosarcomas revealed an expression of EGFR. EGFR expression showed a dose-response relation with improved event-free and overall survival. This was independent of the degree of tumor regression due to neoadjuvant chemotherapy. Nine of 39 (23%) osteosarcomas showed egfr amplifications by means of fluorescence in situ hybridization. All these cases expressed EGFR. When comparing EGFR expression between primary biopsy and resection specimen (n=19), viable residual tumor cells in resection specimens revealed a lower EGFR expression and a tendency toward membranous staining compared with the initial biopsy.
  
  
  CONCLUSIONS
  In conclusion, expression and amplification of EGFR are frequently observed in high-grade osteosarcomas and are associated with improved prognosis in a dose-responsive way. This implies that low EGFR expression possibly predicts lack of response to conventional treatment in high-grade osteosarcomas and may warrant a more intensive therapeutic approach, although not based on EGFR targeting.
authors.affiliation: Institute of Pathology, University of Münster, Münster, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kersting
authors.forename: Carsten
authors.initials: C
authors.lastname: Gebert
authors.forename: Konstantin
authors.initials: K
authors.lastname: Agelopoulos
authors.forename: Hartmut
authors.initials: H
authors.lastname: Schmidt
authors.forename: Paul J
authors.initials: PJ
authors.lastname: van Diest
authors.forename: Heribert
authors.initials: H
authors.lastname: Juergens
authors.forename: Winfried
authors.initials: W
authors.lastname: Winkelmann
authors.forename: Matthias
authors.initials: M
authors.lastname: Kevric
authors.forename: Georg
authors.initials: G
authors.lastname: Gosheger
authors.forename: Burkhard
authors.initials: B
authors.lastname: Brandt
authors.forename: Stefan
authors.initials: S
authors.lastname: Bielack
authors.forename: Horst
authors.initials: H
authors.lastname: Buerger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality*; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D012516:Osteosarcoma / Q000175:diagnosis* / Q000188:drug therapy / Q000401:mortality*; D011379:Prognosis; D013534:Survival
chemical_list: D066246:ErbB Receptors