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

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.

Assessing and validating housekeeping genes in normal, cancerous, and polycystic human ovaries

“…Our results suggest RPL37A, PPIA, and RPS17 to be the most stable HKGs in expression levels in the human ovary. RPL37A was also provided by Siemens Healthcare Diagnostics (Cologne, Germany) for use by Sinn et al [28] in their studies on patients with high-stage, high-grade serous adenocarcinomas, consistent with the general population of ovarian cancer patients in their study. Looking into the literature and HKG studies in human ovaries, our findings on PPIA appear to corroborate those of Yan-Li et al [29], who suggested PPIA as a reference gene in postmenopausal ovaries and serous ovarian cancer subtypes.…”

Does tumour biology determine surgical success in the treatment of epithelial ovarian cancer? A systematic literature review

“…The data are summarised in Supplementary Table 2. Increased gene expression of IGF1R (An et al , 2009), insulin-like growth factor-2 promoter transcripts (Lu et al , 2006), vascular endothelial growth factor C (VEGF-C) (Sinn et al , 2009), SRA1 (Leoutsakou et al , 2006), transforming growth factor-beta 1 (TCGF β 1) (Komiyama et al , 2011), Coxsackie-adenovirus receptor isoforms (CAR3/7 CAR4/7) (Reimer et al , 2007) and lower gene expression of the RNAse III enzyme Drosher (Merritt et al , 2008) have all been found to be associated with suboptimal debulking. It is of note that the studies vary in genes investigated promoter transcripts and definitions of optimal and suboptimal debulking.…”

Serum Vascular Endothelial Growth Factor (VEGF-C) as a Diagnostic and Prognostic Marker in Patients with Ovarian Cancer

“…Data focusing on lymphangiogenesis in ovarian cancer are scant. However, Sinn BV, et al , demonstrated that VEGF-C mRNA is associated with aggressive tumor behavior in ovarian cancer [24]. Although, an increase in VEGF-C mRNA was observed, the relationship between serum VEGF-C levels and tumor behavior has not yet been determined by a quantitative method in vivo.…”