Carcinoma of an unknown primary: are EGF receptor, Her-2 neu, and c-Kit tyrosine kinases potential targets for therapy?

• Published in: British journal of cancer 2007-10, Vol.97 (7), p.857-861
• Main Authors: Massard, C, Voigt, J-J, Laplanche, A, Culine, S, Lortholary, A, Bugat, R, Theodore, C, Priou, F, Kaminsky, M-C, Lesimple, T, Pivot, X, Coudert, B, Douillard, J-Y, Merrouche, Y, Fizazi, K
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies; Biological and medical sciences; Biomarkers, Tumor - metabolism; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cancer therapies; Carcinoma, Papillary; Carcinoma, Papillary - metabolism; Carcinoma, Papillary - pathology; Chemotherapy; Clinical Study; Drug Resistance; Epidemiology; Female; Humans; Immunology; Kinases; Life Sciences; Lymphatic system; Male; Medical prognosis; Medical research; Medical sciences; Medicine; Melanoma; Metastasis; Middle Aged; Molecular Medicine; Neoplasm Staging; Neoplasms, Unknown Primary; Neoplasms, Unknown Primary - metabolism; Neoplasms, Unknown Primary - pathology; Oncology; Prognosis; Prospective Studies; Proteins; Proto-Oncogene Proteins c-kit; Proto-Oncogene Proteins c-kit - metabolism; Receptor, Epidermal Growth Factor; Receptor, Epidermal Growth Factor - metabolism; Receptor, erbB-2; Receptor, ErbB-2 - metabolism; Survival Rate; Tumor Markers, Biological; Tumors
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6603942

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