Abstract 5138: Expression and circulating levels of VEGFC/VEGFD and their receptor VEGFR2, R3 in renal cell cancer: Relationship with clinicopathological parameters

Abstract

Abstract Background: Vascular endothelial growth factors C, VEGF-D and VEGFR-2, R-3, are overexpressed in different malignancies and associated with lymph node metastasis and poor prognosis. In renal cell cancer (RCC) lymphatic tumor spread exists but data focusing on lymphangiogenesis are rare. Since the VEGF-C/VEGF-D/VEGFR-2, R-3 axis appears to be the signaling pathway for tumor-induced lymphangiogenesis and an attractive target for therapeutic intervention; we analyzed the expression and the presence of the soluble forms in 30 non treated metastatic RCC patients and results were correlated with clinicopathological parameters. Methods: Tumor and sera from 30 metastatic renal cell cancer patients (20 clear cell (ccRCC)&10 papillary (pRCC) were included in this study. The expressions of VEGFR-2,R-3 &VEGF-C,-D expressions on tumor were evaluated by immunohistochemestry. Using ELISA assays, soluble vegfr-2–3 &sVEGF-C,-D were measured in sera of RCC patients in comparison to 20 healthy controls. Results: In overall patients, a high expression of VEGF-C,-D and their receptors were observed in more than 55% of the patients as compared to the negative control. Regarding circulating VEGF-C,-D, R2, R-3 they were variable in all samples from either patients or healthy donors. Only median sVEGF- R3 level was significantly higher (p=0.005) in RCC patients as compared to healthy donors. VEGF-C and VEGF-D expression was significantly correlated (r’=0.43, p=0.02) with each other but not with the expression of its receptors. An inverse correlation between Flt-4 expression & its soluble form was noted (r=−0.33 p=0.040). The expression of VEGF-C, VECF-D and sVEGFR-3 were significantly higher in pRCC than ccRCC (p=0.02, 0.01 and 0.035 respectively). The expression of VEGFR-2, VEGFR-3 were not different between the subgroups (p=0.11). Furthermore, no correlation with clinicopathological parameters was shown in either overall patients or in the two subgroups. Conclusions: we showed that in RCC the lymphangiogenic factors are expressed or present as soluble form, a different expression pattern in ccRCC and pRCC existe. Therefore, further studies are necessary to determine if lymphangiogenesis can play a role as a prognostic tool or a target for therapeutic intervention in renal cell carcinoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5138. doi:10.1158/1538-7445.AM2011-5138