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Randomized Controlled Trial
. 2007 Oct 8;97(7):857-61.
doi: 10.1038/sj.bjc.6603942. Epub 2007 Sep 18.

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

C Massard  1 , J-J Voigt, A Laplanche, S Culine, A Lortholary, R Bugat, C Theodore, F Priou, M-C Kaminsky, T Lesimple, X Pivot, B Coudert, J-Y Douillard, Y Merrouche, K Fizazi
Affiliations
Randomized Controlled Trial

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

C Massard et al. Br J Cancer. .

Erratum in

  • Br J Cancer. 2008 Dec 2;99(11):1959

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.

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Figures

Figure 1
Figure 1
Immunohistochemical patterns of EGFR expression in a carcinomas of an unknown primary site (CUP) specimen showing strong EGFR immunostaining (magnification × 400).
Figure 2
Figure 2
Immunohistochemical patterns of Her-2/neu expression in a carcinomas of an unknown primary site (CUP) specimen showing strong HER-2/neu immunostaining (magnification × 400).
Figure 3
Figure 3
Immunohistochemical patterns of c-Kit expression in a carcinomas of an unknown primary site (CUP) specimen showing strong c-Kit immunostaining (magnification × 400).
See this image and copyright information in PMC

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