Expression of vascular endothelial growth factor and microvessel density in head and neck tumorigenesis

Angiogenesis is a fundamental process in tumor growth and metastasis, and i ts significance and that of vascular endothelial growth factor (VEGF) expre ssion as prognostic indicators have been documented for various types of hu man tumors. However, the mechanisms responsible for angiogenesis in head an d neck squamous cell carcinoma are not well defined. To examine the relatio nship between angiogenesis and the phenotypic progressions of head and neck tumorigenesis, we used immunohistochemistry to analyze VEGF expression and microvessel density in 70 paraffin-embedded specimens that contained adjac ent normal epithelium, premalignant lesions, or both from 57 patients with head and neck squamous cell carcinoma. Ten samples of normal oral mucosa we re obtained from people who did not smoke or drink alcohol and included in the analysis as normal controls. Microvessel density was evaluated by avera ging 10 microscopic fields (x 400) in a defined area of each specimen. The degree of VEGF expression was assessed on a cell-by-cell basis in 10 micros copic fields (x 200) in a defined area on a scale ranging from 0 (no expres sion) to 3+ (highest level of expression). In addition, the weighted mean i ndex of VEGF expression was calculated, The mean +/- SD weighted mean index of VEGF expression in normal control epithelium (1.10 +/- 0.38, n = 10) wa s higher than it was in adjacent normal epithelium (0.82 +/- 0.27, n = 13; P = 0.04), VEGF expression decreased as samples ranged from normal adjacent epithelium to hyperplasia (0.78 +/- 0.28, n = 21), mild dysplasia (0.70 +/ - 0.29, n = 28), moderate dysplasia (0.67 +/- 0.29, n = 11), severe dysplas ia (0.51 +/- 0.39, n = 6), and squamous cell carcinoma (0.20 +/- 0.27, n = 70; overall P = 0.0001). VEGF expression was two times lower in cases with nodal disease (0.17 +/- 0.26, n = 29) than it was in nonnodal disease (0.32 +/- 0.29, n = 16; P = 0.02), Microvessel density showed no significant dif ference from adjacent normal epithelium premalignant lesions to cancer. In tumor, no correlation was seen between VEGF expression or microvessel densi ty and differentiation, primary tumor site, T stage, or smoking status. The se findings indicate that VEGF expression is down-regulated during head and neck tumorigenesis, However, further studies are required to better unders tand the mechanism of VEGF down-regulation in head and neck tumorigenesis.