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Epidermal Growth Factor Receptor Expression in High-Grade Osteosarcomas Is Associated with a Good Clinical Outcome

Authors' Affiliations: ¹ Institute of Pathology and ² Department of Orthopedic Surgery, University of Münster; ³ Department of Pediatric Hematology and Oncology, University Children's Hospital Münster, Münster, Germany; ⁴ Department of Pathology, University of Utrecht, Utrecht, the Netherlands; ⁵ Institute of Tumour Biology, University of Hamburg, Hamburg, Germany; and ⁶ Olgahospital Stuttgart, Pediatrics 5 (Oncology, Hematology, Immunology), and ⁷ Institute of Pathology, Paderborn, Germany

Requests for reprints: Horst Buerger, Institute of Pathology, University of Münster, Albert-Schweitzer-Strasse 33, 48149 Münster, Germany. Phone: 49-2-51-83-55450; Fax: 49-2-51-83-55460; E-mail: buerger{at}histopatho.eu.

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.