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. Sinn1
, 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.
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