1. ¹Department of Medicine, Institut Gustave Roussy, 39 rue Camille Desmoulins, Villejuif 94805, France
2. ²Department of Pathology, Centre Claudius Regaud, Toulouse, France
3. ³Department of Statistics, Institut Gustave Roussy, Villejuif, France
4. ⁴Department of Medicine, Centre Val d'Aurelle, Montpellier, France
5. ⁵Department of Medicine, Centre Paul Papin, Anger, France
6. ⁶Department of Medicine, Institut Claudius Regaud, Toulouse, France
7. ⁷Department of Medicine, Centre Hospitalier La Roche/Yon, La Roche/Yon, France
8. ⁸Department of Medicine Centre Alexis Vautrin, Nancy, France
9. ⁹Department of Medicine, Centre Eugène Marquis, Rennes, France
10. ¹⁰Department of Medicine, Centre Hospitalier Universitaire, Besançon, France
11. ¹¹Department of Medicine, Centre G.F. Leclerc, Dijon, France
12. ¹²Department of Medicine, Centre René Gauducheau, Nantes, France
13. ¹³Department of Medicine, Institut de Cancérologie de la Loire, Saint-Etienne, France

Correspondence: Dr C Massard, E-mail: christophe.massard@igr.fr

Received 22 March 2007; Revised 13 July 2007; Accepted 20 July 2007; Published online 18 September 2007.

Abstract

Carcinomas of an unknown primary site (CUP) are heterogeneous tumours with a median survival of only 8 months. Tyrosine kinase inhibitors are promising new drugs. The aim of this study was to determine the expression of EGF-receptor, Her-2/neu, and c-Kit tyrosine kinases in CUP. Paraffin-embedded specimens were obtained from 54 patients with a CUP who were included in the GEFCAPI 01 randomised phase II trial. Immunohistochemistry was performed using the Dako autostainer with antibodies directed against HER-2/neu protein, EGFR protein, and c-Kit protein (CD117). EGFR expression was found in 36 out of 54 samples (66%). In contrast, Her-2/neu overexpression and c-Kit positivity were only detected in 4 and 10% of patients, respectively. No significant association was found between the expression of the tyrosine kinase receptors and prognosis. EGFR expression was significantly associated with response to cisplatin-based chemotherapy: the response rates were 50 and 22% in patients with EGFR-positive tumours and EGFR-negative tumours, respectively (P<0.05). This study shows that EGFR is frequently expressed in CUP. This finding may prompt clinical trials investigating EGFR inhibitors in this setting. In contrast, c-Kit expression and Her-2/neu overexpression occur infrequently in CUP. EGFR expression was correlated to tumour chemosensitivity.