Abstract 381: VEGF-A and VEGF-C: potential coregulators in angiogenic event in thyroid cancer.

Abstract

Vascular endothelial growth factor (VEGF) promotes growth of blood or lymphatic vessels, termed angiogenesis and lymphangiogenesis. These share several basal mechanisms, including cross-talk between VEGF-A, C and their receptors, which may be important in the development of malignancies. Study aimed to identify relationships between VEGF-A, VEGF-C and their impact in angiogenesis and metastases in thyroid cancers.We studied VEGF-A and VEGF-C mRNA expression in 123 thyroid cancers, 40 lymph node metastases and 7 non-malignant thyroid control tissues using qPCR. Protein expressions for both VEGFs were determined by immunohistochemistry.VEGF-A and VEGF-C mRNA over-expression was noted in 51% (n=62) and 27% (n=33) of the thyroid cancers respectively. VEGF-A and VEGF-C protein over-expression was also identified in 70% (n=86) and 62% (n=76) of the thyroid cancers. ANOVA showed significant expression differences for VEGF-A and VEGF-C in subtypes of thyroid carcinoma, lymph node metastasis and normal controls (P=1x10-6 and 1x10-5 respectively). VEGF-A mRNA was significantly higher in cancers with lymph node metastases compared to non-metastatic cancers (p=0.001) however, most metastatic tumors under-expressed VEGF-C (p=0.0002). Similarly, VEGF-A protein expression was higher in metastases and VEGF-C protein was higher in non-metastatic lesions, though not significantly. Finally, we used linear regression analysis to test previous proposals about physiological interactions of VEGF-A and VEGF-C expression. Our model indicated that in metastatic cancers, 32% of the expression of VEGF-A could be predicted by a positive influence of VEGF-C production (model p=0.0002). These findings add weight to previous hypotheses concerning VEGF-A and C interaction. Early lymphangiogenic events were proposed to regulate angiogenesis, and changes to VEGF expression in this cancer population bear this out, with VEGF-C in early tumors giving way to VEGF-A in metastases. The commonality of local metastasis in thyroid cancer makes it a useful model to further examine mechanisms of angiogenesis and lymphangiogenesis in cancer metastasis. Keywords: thyroid cancer, VEGF-A, VEGF-C Citation Format: Ali Salajegheh, Robert A. Smith, Sahar Pakneshan, Vinod Gopalan, Alfred KY Lam. VEGF-A and VEGF-C: potential coregulators in angiogenic event in thyroid cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 381. doi:10.1158/1538-7445.AM2013-381