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

Objective/Hypothesis: Angiogenesis has been used as a prognostic indicator in a variety of cancers and is believed to be controlled by angiogenic fact ors, 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 gr owth and metastasis by enhancing angiogenesis, Methods: Immunohistochemical analysis for IL-8 and VEGF was performed using specimens from 33 cancer pa tients and 6 control patients. We quantitatively evaluated levels of IL-8 a nd VEGF in tumor tissue homogenates from those same patients using enzyme-l inked immunosorbent assay and radioimmunoassay. Comprehensive histories of each patient were taken and later analyzed for clinical correlations with I L-8 or VEGF levels. Results: IL-8 and VEGF were found to be colocalized wit hin the head and neck squamous cell carcinoma (HNSCCA) tumor cells, in the head and neck tumor specimens, IL-8 levels ([38,152 +/- 1.8] x 10(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 fou rfold higher than the controls (317 +/- 400 pg/mg TP), Interleukin-8 and VE GF levels were found to have a positive correlation (P less than or equal t o .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 sh orter disease-free intervals (P less than or equal to .03) Conclusions: Mar ked 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.