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Original Article

Vascular endothelial growth factor C mRNA expression is a prognostic factor in epithelial ovarian cancer as detected by kinetic RT-PCR in formalin-fixed paraffin-embedded tissue

Bruno V. SinnContact Information, Silvia Darb-Esfahani1, Ralph M. Wirtz2, Areeg Faggad1, Wilko Weichert1, Ann-Christin Buckendahl1, Aurelia Noske1, Berit Maria Müller1, Jan Budczies1, Jalid Sehouli3, Elena I. Braicu3, Manfred Dietel1 and Carsten Denkert1

(1)  Institute of Pathology, Charité Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117 Berlin, Germany
(2)  Siemens Healthcare Diagnostics, Cologne, Germany
(3)  Department of Gynaecology and Obstetrics, Charité Universitätsmedizin Berlin, Berlin, Germany

Received: 31 July 2009  Revised: 24 September 2009  Accepted: 21 October 2009  Published online: 13 November 2009

Abstract  Vascular endothelial growth factor C (VEGF-C) is a well described chemotactic and growth factor for lymphatic endothelial cells. Its inhibition leads to suppression of lymphatic and distant metastases in mouse models. In ovarian cancer, the relationship between VEGF-C expression and tumor behavior has not yet been determined by a quantitative method in vivo. Therefore, we used a new technique of RNA extraction from formalin-fixed paraffin-embedded tissue samples and determined the expression levels of VEGF-C mRNA in a study group of 97 ovarian cancer patients. Expression levels were correlated with clinicopathological features and patient survival. High VEGF-C expression was associated with worse overall (p = 0.0393) and progression-free (p = 0.0155) patient survival. In the subgroups of serous tumors and high-grade tumors, VEGF-C mRNA was still a negative indicator for patient survival (p = 0.0190 and 0.0311, respectively). A trend was observed among patients with high clinical stage (p = 0.0634). In multivariate survival analysis VEGF-C mRNA retained its prognostic influence on progression-free survival (p = 0.006, HR = 0.319 with a 95% confidence interval of 0.142–0.720). High VEGF-C expression was further associated with an increased residual tumor mass after primary cytoreductive surgery. We found no correlation of VEGF-C expression with tumor grade, FIGO stage, lymph node, or distant metastases. Our study demonstrates that high VEGF-C expression is associated with aggressive tumor behavior in ovarian cancer. mRNA extracted from paraffin-embedded tumor samples is suitable for VEGF-C gene expression studies.

Keywords  VEGF-C - FFPE tissue - Ovarian cancer - Lymphangiogenesis

Bruno V. Sinn and Silvia Darb-Esfahani contributed equally to the publication.

Contact Information Bruno V. Sinn
Email: bruno.sinn@charite.de
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