Vascular Endothelial Growth Factor Expression Correlates with p53 Mutation and Angiogenesis in Squamous Cell Carcinoma of the Head and Neck

Abstract

Vascular endothelial growth factor (VEGF) has potent angiogenic activity and has been identified in a wide variety of malignancies, including head and neck squamous cell carcinoma (HNSCC). The tumour-suppressor gene p53 has been thought to regulate VEGF. Cryostat sections of 33 head and neck squamous cell carcinomas (HNSCC) were immunostained for VEGF using a standard streptavidin-biotin complex procedure. To evaluate angiogenesis, microvascular density was counted by staining endothelial cells immunohistochemically using anti-vWF monoclonal antibody. The p53 gene status was analysed using a PCR-SSCP analysis and direct sequencing. VEGF positive staining was detected in 18 (55%) out of 33 tumours. VEGF immunoreactivity did not correlate with the main clinicopathological characteristics of the patients (localization, T-stage, N-status, histological grading). Statistical analysis gave a clear correlation between the tumour vascularity and the VEGF protein expression (p = 0.0036). VEGF negative tumours showed a lower mean number of microvessels per microscopic field (60.3 +/- 15.5) than VEGF positive tumours (79.6 +/- 22.9). P53 mutations were identified in 12 (36.4%) of 33 tumours. The 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 the hypothesis of a p53 regulation on the angiogenic process through a VEGF up-regulation.

Immunohistochemical Coexpression of VEGF and CD34 in Ameloblastoma

“…This accrued a convincing evidence reported in our study concerning the association of VEGF over expression with the MvD. Similar strong correlation was shown in other studies in oral SCC ( 23,24).…”

Prostaglandin-endoperoxide synthase 2 (PTGS2) gene expression and its association with genes regulating the VEGF signaling pathway in head and neck squamous cell carcinoma

“… 27 Though PTGS2 expression was found to be higher in TP53 mutant cells, clinically, no correlation has been found between the two factors in disease progression and survival. 28 Several studies support the hypothesis that p53 regulates the angiogenesis process via the expression of VEGF 29 ; parallelly, in this study, a similar expression pattern was observed where the expression of VEGFA and VEGFB was higher in tumor samples with TP53 mutations.…”

MRI features predict p53 status in lower-grade gliomas via a machine-learning approach

“…In the current study, the most predictive features of p53 status were selected based on the LASSO algorithm, and the biological correlations between these features and p53 status could also be revealed preliminarily. For example, it was reported that the microvessel count is higher in p53-mutated tumors than in p53-wildtype tumors ( Guo et al, 2008 ), as the vascular endothelial growth factor is overexpressed in p53-mutated tumors ( Riedel et al, 2000 , Uchida et al, 1998 ). Differences in microvascularity could result in differences in signal on T2 weighted images due to differences in water content ( Dang et al, 2015 ), which could explain why Maximum_6 and Median_6 are higher in p53-mutant tumors than those in p53-wildtype tumors.…”