Role of angiogenic factors: Coexpression of interleukin‐8 and vascular endothelial growth factor in patients with head and neck squamous carcinoma

Abstract

Angiogenesis has been used as a prognostic indicator in a variety of cancers and is believed to be controlled by angiogenic factors, including the cytokines interleukin-8 (IL-8) and vascular endothelial growth factor (VEGF). We hypothesized that the in vivo coexpression of both IL-8 and VEGF in head and neck tumors contributes to perpetuating tumor growth and metastasis by enhancing angiogenesis. Immunohistochemical analysis for IL-8 and VEGF was performed using specimens from 33 cancer patients and 6 control patients. We quantitatively evaluated levels of IL-8 and VEGF in tumor tissue homogenates from those same patients using enzyme-linked immunosorbent assay and radioimmunoassay. Comprehensive histories of each patient were taken and later analyzed for clinical correlations with IL-8 or VEGF levels. IL-8 and VEGF were found to be colocalized within the head and neck squamous cell carcinoma (HNSCCA) tumor cells. In the head and neck tumor specimens, IL-8 levels ([38,152+/-1.8]x10(5) pg/mg total protein [TP]) were 22-fold greater than controls (1,721+/-2,122 pg/mg TP). The tumor levels of VEGF (1,304+/-6,037 pg/mg TP) were nearly fourfold higher than the controls (317+/-400 pg/mg TP. Interleukin-8 and VEGF levels were found to have a positive correlation (P< or = .0001). Patients exhibiting high levels in picograms per milligram of TP and/or number of moles of IL-8 and VEGF were found to clinically have more aggressive disease manifested by higher TNM stage, more recurrences, and shorter disease-free intervals (P< or =.03) Marked increase in HNSCCA of IL-8 and VEGF underscores the importance of these angiogenic factors in this disease. Understanding the roles and interplay of angiogenic factors such as IL-8 and VEGF may have value in the treatment of HNSCCA.