The Relationship of Vascular Endothelial Growth Factor and Coagulation Factor (Fibrin and Fibrinogen) Expression in Clear Cell Renal Cell Carcinoma

Objectives: To investigate the relationship between angiogenesis and coagulation markers in tumor tissues of primary renal cell carcinoma (RCC). Tumors stimulate angiogenesis and activate the coagulation cascade. The importance of the interplay between these pathways for RCC is unknown. Methods: In all, 69 clear cell RCC specimens were analyzed by immunohistochemical staining applied to tissue microarrays. The expression of vascular endothelial growth factor (VEGF), hypoxia-inducible factor-1α, fibrinogen and fibrin, and microvessel density were visually analyzed. Finally, staining patterns were related to clinical variables and survival. Results: The VEGF expression was detected in 100% of tumors, with 68% showing a high expression, whereas hypoxia-inducible factor-1α staining was low (only 26% had a moderate to high staining). Fibrinogen was expressed adjacent to the tumor cells in 26% of cases, whereas in 84% it was expressed around the blood vessels. In 30% of tumors, expression of fibrin was detected. High tumor VEGF expression correlated with high fibrin staining (P = .05). From a multivariate analysis, microvessel density (P = .033) and fibrinogen adjacent to tumor cells (P = .046) were independent factors related to VEGF expression. Conclusions: In this study, we found clinical evidence for the permeability activity of VEGF as reflected by extravascular fibrinogen expression adjacent to tumor cells in the extracellular matrix. In addition, VEGF and fibrin expression were associated, indicative for concomitant activation of the coagulation cascade and angiogenesis in RCC. Taken together, these data indicate that activation of angiogenesis and coagulation are related in RCC.