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Prognostic Significance of Vascular Endothelial Growth Factor Immunohistochemical Expression in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis

¹ Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine; ² Biomedical Research Institute, Foundation for Research and Technology-Hellas, Ioannina, Greece; ³ Medical Research Center Hospital do Cancer, Sao Paulo, Brazil; and ⁴ Institute for Clinical Research and Health Policy Studies, Department of Medicine, Tufts-New England Medical Center, Tufts University School of Medicine Boston, Boston, Massachusetts

Requests for reprints: John P.A. Ioannidis, Department of Hygiene and Epidemiology, University of Ioannina School of Medicine, Ioannina 45110, Greece. Phone: 30-26510-97807; Fax: 30-26510-97867. E-mail: jioannid{at}cc.uoi.gr.

Purpose: Vascular endothelial growth factor (VEGF) is considered as a prime mediator of angiogenesis. Various studies examining the relationship between VEGF protein overexpression with the clinical outcome in patients with head and neck squamous cell carcinoma have yielded inconclusive results.

Experimental Design: We conducted a meta-analysis of 12 studies (n = 1.002 patients) that evaluated the correlation between VEGF (detected by immunohistochemistry) and 2-year overall survival. The relation between VEGF and lymph node involvement (11 studies, n = 722) was also examined. Data were synthesized with random effect and fixed effect risk ratios.

Results: The estimated risk of death in 2 years was 1.88-fold higher in the VEGF-positive patients [95% confidence interval, 1.43-2.45; P < 0.001 random effect calculations]. Between-study heterogeneity was nonsignificant (P = 0.15) but larger studies tended to provide more conservative estimates (P = 0.097). VEGF overexpression was not significantly associated with the presence of lymph node metastasis (risk ratio, 1.20; 95% confidence interval, 0.97-1.49; P = 0.087) and there was significant between-study heterogeneity (P = 0.08).

Conclusions: Although some modest bias cannot be excluded, VEGF positivity seems to be associated with worse overall survival in patients with head and neck squamous cell carcinoma.

Key Words: VEGF • head and neck squamous cell carcinoma • angiogenesis • survival • meta-analysis

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