Pitfalls in immunohistochemical assessment of EGFR- expression in soft tissue sarcomas

¹ Institute of Pathology, University of Muenster, Germany, Germany
² Institute of Pathology, University of Muenster, Muenster, Germany, Germany
³ Department of Orthopaedic Surgery, Germany
⁴ Institute of Clinical Chemistry and Laboratory Medicine, University of Muenster, Muenster, Germany, Germany
⁵ Institute of Pathology, Medizinische Hochschule Hannover, Hannover, Germany, Germany
⁶ Department of Orthopaedic Surgery, University of Muenster, Muenster, Germany, Germany
⁷ 5Department of Pathology, University Medical Center Utrecht, Utrecht, The Netherlands, Netherlands

^* To whom correspondence should be addressed. E-mail: burgerh{at}uni-muenster.de.

Accepted 28 June 2005

	Abstract

Aims: New targeted cancer therapies acting against growth factor receptors such as the Epidermal Growth Factor Receptor (EGFR) necessitate selecting patients for treatment with these drugs. Besides carcinomas, soft tissue sarcomas (STS) express EGFR and might thereby be a promising target for this new therapeutic strategy.

Methods: We examined 302 specimens of STS using the tissue microarray technique. EGFR expression levels were assessed with immunohistochemistry using five different commercially available antibodies. With fluorescence in situ hybridisation (FISH), gene amplification status was measured. Immunoreactivity and amplification status were correlated with clinicopathologic features and follow up data available for 163 cases.

Results: EGFR expression frequency ranged between 0.3% and 52.9% depending on antibody and scoring method used. 3.5% of the tumors exhibited egfr gene amplification by FISH which correlated with EGFR expression for 3 antibodies. Only one antibody had independent prognostic value in multivariate analysis and correlated with unfavourable outcome. egfr gene amplification status showed no correlations with clinical features.

Conclusions: Frequency of EGFR immunopositivity in STS strongly depends on the antibody used, and only one of 5 tested antibodies predicted unfavourable clinical outcome. This indicates that choice of primary antibody and scoring system have substantial impact on determination of EGFR immunoreactivity.

Key Words: amplification, egfr, immunohistochemistry, prognosis, soft tissue sarcoma

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