TY - JOUR
T1 - Carcinoma of an unknown primary
T2 - Are EGF receptor, Her-2/neu, and c-Kit tyrosine kinases potential targets for therapy?
AU - Massard, C.
AU - Voigt, J. J.
AU - Laplanche, A.
AU - Culine, S.
AU - Lortholary, A.
AU - Bugat, R.
AU - Theodore, C.
AU - Priou, F.
AU - Kaminsky, M. C.
AU - Lesimple, T.
AU - Pivot, X.
AU - Coudert, B.
AU - Douillard, J. Y.
AU - Merrouche, Y.
AU - Fizazi, K.
PY - 2007/10/8
Y1 - 2007/10/8
N2 - 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.
AB - 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.
KW - Carcinoma of an unknown primitive
KW - EGFR
KW - Her-2/neu overexpression
KW - Tyrosine kinase receptor
KW - c-Kit
UR - http://www.scopus.com/inward/record.url?scp=34948816642&partnerID=8YFLogxK
U2 - 10.1038/sj.bjc.6603942
DO - 10.1038/sj.bjc.6603942
M3 - Article
C2 - 17876336
AN - SCOPUS:34948816642
SN - 0007-0920
VL - 97
SP - 857
EP - 861
JO - British Journal of Cancer
JF - British Journal of Cancer
IS - 7
ER -