Epidermal growth factor receptor expression in high-grade osteosarcomas is associated with a good clinical outcome.
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Epidermal growth factor receptor expression in high-grade osteosarcomas is associated with a good clinical outcome. / Kersting, Christian; Gebert, Carsten; Agelopoulos, Konstantin; Schmidt, Hartmut; Diest, van; Paul, J; Juergens, Heribert; Winkelmann, Winfried; Kevric, Matthias; Brandt, Burkhard; Brandt, Burkhard; Bielack, Stefan; Buerger, Horst.
In: CLIN CANCER RES, Vol. 13, No. 10, 10, 2007, p. 2998-3005.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 - Diest, van
AU - Paul, J
AU - Juergens, Heribert
AU - Winkelmann, Winfried
AU - Kevric, Matthias
AU - Brandt, Burkhard
AU - Brandt, Burkhard
AU - Bielack, Stefan
AU - Buerger, Horst
PY - 2007
Y1 - 2007
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.
M3 - SCORING: Zeitschriftenaufsatz
VL - 13
SP - 2998
EP - 3005
JO - CLIN CANCER RES
JF - CLIN CANCER RES
SN - 1078-0432
IS - 10
M1 - 10
ER -