Epidermal growth factor receptor expression in high-grade osteosarcomas is associated with a good clinical outcome

Christian Kersting, Carsten Gebert, Konstantin Agelopoulos, Hartmut Schmidt, Paul J. Van Diest, Heribert Juergens, Winfried Winkelmann, Matthias Kevric, Georg Gosheger, Burkhard Brandt, Stefan Bielack, Horst Buerger

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: 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. Experimental Design: 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.

Original languageEnglish (US)
Pages (from-to)2998-3005
Number of pages8
JournalClinical Cancer Research
Volume13
Issue number10
DOIs
StatePublished - May 15 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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