Vascular endothelial growth factor expression correlates with p53 mutationand angiogenesis in squamous cell carcinoma of the head and neck

Vascular endothelial growth factor (VEGF) has potent angiogenic activity an d has been identified in a wide variety of malignancies, including head and neck squamous cell carcinoma (HNSCC). The tumour-suppressor gene p53 has b een thought to regulate VEGF. Cryostat sections of 33 head and neck squamou s cell carcinomas (HNSCC) were immunostained for VEGF using a standard stre ptavidin-biotin complex procedure. To evaluate angiogenesis, microvascular density was counted by staining endothelial cells immunohistochemically usi ng anti-vWF monoclonal antibody. The p53 gene status was analysed using a P CR-SSCP analysis and direct sequencing. VEGF positive staining was detected in 18 (55%) out of 33 tumours. VEGF immunoreactivity did not correlate wit h the main clinicopathological characteristics of the patients (localizatio n, T-stage, N-status, histological grading). Statistical analysis gave a cl ear correlation between the tumour vascularity and the VEGF protein express ion (p = 0.0036). VEGF negative tumours showed a lower mean number of micro vessels per microscopic held (60.3 +/- 15.5) than VEGF positive tumours (79 .6 +/- 22.9). P53 mutations were identified in 12 (36.4%) of 33 tumours. Th e association of p53 mutations and VEGF expression level was significant (0 .027). The higher microvessel density in VEGF positive tumours supports the importance of VEGF for tumour angiogenesis in HNSCC. Our results support t he hypothesis of a p53 regulation on the angiogenic process through a VEGF up-regulation.