Molecular Diagnostics
British Journal of Cancer (2007) 96, 485–491. doi:10.1038/sj.bjc.6603581 www.bjcancer.com
Published online 23 January 2007
In ovarian cancer the prognostic influence of HER2/neu is not dependent on the CXCR4/SDF-1 signalling pathway
D Pils1, A Pinter1, J Reibenwein1, A Alfanz1, P Horak1, B C Schmid2, L Hefler2, R Horvat3, A Reinthaller2, R Zeillinger2 and M Krainer1
- 1Department of Internal Medicine I, Division of Oncology, Medical University of Vienna, Waehringer Guertel 18-20, Vienna A-1090, Austria
- 2Department of Obstetrics and Gynecology, Division of Gynecology, Medical University of Vienna, Vienna 1090, Austria
- 3Clinical Pathology, Medical University of Vienna, Vienna 1090, Austria
Correspondence: Professor M Krainer, E-mail: michael.krainer@meduniwien.ac.at
Revised 14 November 2006; Accepted 11 December 2006; Published online 23 January 2007.
Abstract
HER2/neu overexpression is a driving force in the carcinogenesis of several human cancers. In breast cancer the prognostic influence of HER2/neu was shown to be at least partly based on increased metastatic potential mediated by the chemokine–chemokine receptor pair SDF-1(CXCL12)/CXCR4. We wanted to evaluate the influence of HER2/neu on ovarian cancer prognosis and to investigate whether compromised survival would correlate with CXCR4 expression and/or SDF-1 abundance. Therefore, we analysed HER2/neu, CXCR4, and SDF-1 in 148 ovarian tumour samples by means of immunohistochemistry on tissue microarrays. Overexpression of HER2/neu was found in 27.6% of ovarian cancer tissues and in 15% of ovarian borderline tumours. In ovarian cancer patients, overexpression of HER2/neu correlated closely with overall survival (univariate hazard ratio (HR) 2.59, P=0.005; multiple corrected HR 1.92, P=0.074). In contrast, CXCR4 expression and SDF-1 abundance had no impact on overall survival, and both parameters were not correlated with HER2/neu expression. As expected, cytoplasmic CXCR4 expression and SDF-1 abundance correlated closely (P<0.0001). Our results confirm a univariate influence of HER2/neu expression on overall survival, which was completely independent of the expression of CXCR4 and the abundance of SDF-1, implying significant differences between the HER2/neu downstream pathways in ovarian cancer compared with breast cancer.
Keywords:
ovarian cancer, immunohistochemistry, tissue microarray, HER2/neu, CXCR4, SDF-1
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