Angiogenesis and the expression of vascular endothelial growth factors A and C in squamous cell carcinoma of the piriform fossa

Background: Angiogenesis is essential for tumor growth and invasion. Vascular endothelial growth factor A (VEGF-A) is a prime mediator of tumor angiogenesis; VEGF-C, another member of the closely related VEGF family of proteins, has major effects on lymphatic endothelial cells and may be important in the process of lymphatic metastasis. Objectives: To evaluate the expression of these cytokines in hypopharyngeal squamous cell carcinoma and to ascertain the effects of these proteins on lymphatic metastasis and vascular angiogenesis. Design: Retrospective analysis of microvessel density and the expression of VEGF-A and VEGF-C. Setting: An academic referral center. Subjects: Thirty-four patients with stage T2 to T4 squamous cell carcinoma of the piriform fossa. Interventions: Expression of VEGF-A and VEGF-C was determined by immunohistochemistry on formalin-fixed, paraffin-embedded biopsy specimens. Angiogenesis was measured as microvessel density by staining endothelial cells for platelet-endothelial cell adhesion molecule 1/CD31. Results: Of the 34 tumors, 21 had clinicoradiologic evidence of lymphatic metastasis. Expression of VEGF-C was associated with lymphatic metastasis (P<.001), but not with microvessel density. The VEGF-A expression correlated with microvessel density (P<.001), but neither VEGF-A expression nor microvessel density was associated with lymphatic metastasis. Conclusions: The expression of VEGF-C is associated with lymphatic metastasis in squamous cell carcinoma of the piriform fossa. This is not secondary to effects on vascular angiogenesis and is hypothesized to be due to effects on lymphatic endothelial cells.