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


METHODS
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.


RESULTS
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)


CONCLUSIONS
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.
Eisma
R J
RJ
Department of Surgery, University of Connecticut Health Center, School of Medicine, Farmington 06030-3105, USA.
Spiro
J D
JD
Kreutzer
D L
DL
D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000098:blood supply / Q000378:metabolism*; D016228:Endothelial Growth Factors / Q000378:metabolism*; D005260:Female; D006258:Head and Neck Neoplasms / Q000098:blood supply / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D016209:Interleukin-8 / Q000378:metabolism*; D008222:Lymphokines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic / Q000502:physiology; D012189:Retrospective Studies; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D016209:Interleukin-8; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors