title: 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.
authors.affiliation: Institute of Pathology, Charité Universitätsmedizin Berlin, Campus Mitte, Charitéplatz 1, 10117, Berlin, Germany. bruno.sinn@charite.de
authors.forename: Bruno V
authors.initials: BV
authors.lastname: Sinn
authors.forename: Silvia
authors.initials: S
authors.lastname: Darb-Esfahani
authors.forename: Ralph M
authors.initials: RM
authors.lastname: Wirtz
authors.forename: Areeg
authors.initials: A
authors.lastname: Faggad
authors.forename: Wilko
authors.initials: W
authors.lastname: Weichert
authors.forename: Ann-Christin
authors.initials: AC
authors.lastname: Buckendahl
authors.forename: Aurelia
authors.initials: A
authors.lastname: Noske
authors.forename: Berit Maria
authors.initials: BM
authors.lastname: Müller
authors.forename: Jan
authors.initials: J
authors.lastname: Budczies
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.forename: Elena I
authors.initials: EI
authors.lastname: Braicu
authors.forename: Manfred
authors.initials: M
authors.lastname: Dietel
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018572:Disease-Free Survival; D005260:Female; D005557:Formaldehyde / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016612:Paraffin Embedding; D011379:Prognosis; D012333:RNA, Messenger / Q000302:isolation & purification / Q000378:metabolism; D016707:Tissue Fixation; D042582:Vascular Endothelial Growth Factor C / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D042582:Vascular Endothelial Growth Factor C; D005557:Formaldehyde