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

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.

• Authors: 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
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 13 Issue 10 Pg. 2998-3005 (May 15 2007) ISSN: 1078-0432 [Print] United States
• PMID: 17505002 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ErbB Receptors

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Bone Neoplasms (diagnosis, drug therapy, mortality)
• Child
• Child, Preschool
• Disease-Free Survival
• ErbB Receptors (analysis, genetics, metabolism)
• Female
• Humans
• In Situ Hybridization, Fluorescence
• Infant
• Infant, Newborn
• Male
• Middle Aged
• Osteosarcoma (diagnosis, drug therapy, mortality)
• Prognosis
• Survival