TY - JOUR
T1 - Epidermal growth factor receptor expression in high-grade osteosarcomas is associated with a good clinical outcome
AU - Kersting, Christian
AU - Gebert, Carsten
AU - Agelopoulos, Konstantin
AU - Schmidt, Hartmut
AU - Van Diest, Paul J.
AU - Juergens, Heribert
AU - Winkelmann, Winfried
AU - Kevric, Matthias
AU - Gosheger, Georg
AU - Brandt, Burkhard
AU - Bielack, Stefan
AU - Buerger, Horst
PY - 2007/5/15
Y1 - 2007/5/15
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-06-2432
DO - 10.1158/1078-0432.CCR-06-2432
M3 - Article
C2 - 17505002
AN - SCOPUS:34249809403
SN - 1078-0432
VL - 13
SP - 2998
EP - 3005
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 10
ER -