Vascular endothelial growth factor (VEGF) expression in oral tissues: possible relevance to angiogenesis, tumour progression and field cancerisation

Abstract

The aim of this study was to assess whether vascular endothelial growth factor (VEGF) expression in oral tissues is associated with angiogenesis, disease progression or field cancerisation. Vascularity and VEGF immunoreactivity were quantified in 68 archival specimens including normal oral mucosa (NOM), dysplasia (DYS) and squamous cell carcinoma (SCC). Vascularity increased significantly with disease progression; it was also higher in NOM adjacent to SCC than in NOM from healthy tissue, suggesting an association with field cancerisation. VEGF expression in epithelial cells was evaluated using two antibodies and three indices. VEGF indices and vascularity were not directly correlated. The expression of VEGF was similar in all DYS and NOM specimens, whether or not adjacent to a concurrent lesion. A comparison of SCC with NOM or DYS led to opposite results, depending on the VEGF antibody and index used. We conclude that VEGF expression in the oral mucosa may play a physiological role, but does not appear to be associated with angiogenesis, field cancerisation or transition to dysplasia. Further studies concerned with tumour development require examining specific VEGF isoforms and standardisation of the methodology.

Angiogenesis in pre-malignant conditions

“…Studies of oral pre-malignant tissue demonstrated a significant increase in MVD with progression from normal epithelium to invasive cancer (Carlile et al, 2001). In a large series of Barrett's oesophagus and associated adenocarcinoma, angiogenesis was markedly increased in pre-malignant lesions, which correlated with VEGF expression.…”

Prognostic significance of vascular endothelial growth factor protein levels in T1‐2 N0 laryngeal cancer treated with primary radiation therapy

“…15,16 VEGF is a 34-50-kD dimmer comprising 2 identical disulfide-linked subunits from differential splicing of a single gene. 9,17,18 VEGF is induced under hypoxic conditions in several tissue types and binds to tyrosine kinase receptors Fly-1 and KDR/ Flk-1 to stimulate angiogenic factors. 9,17,18 Those tissues that overexpress VEGF may be associated with portions of tumors that are biologically radioresistant and correlate with poor local control and overall survival.…”

“…9,17,18 VEGF is induced under hypoxic conditions in several tissue types and binds to tyrosine kinase receptors Fly-1 and KDR/ Flk-1 to stimulate angiogenic factors. 9,17,18 Those tissues that overexpress VEGF may be associated with portions of tumors that are biologically radioresistant and correlate with poor local control and overall survival. In 2000, Smith et al reported VEGF expression as an independent risk factor for poor local and overall survival in head and neck squamous cell carcinoma (HNSCC).…”

Immunohistochemical Analysis of Vascular Endothelial Growth Factor (VEGF) Expression and Tumor Angiogenesis in Tongue Squamous Cell Carcinomas.

“…Activities of VEGF include enhancement of both angiogenesis and vascular permeability (9,10,12,14). VEGF is synthesized and secreted by many types of tumors, and expression levels of VEGF correlate with tumor status and prognosis (14,(15)(16)(17)(18)(19).…”

“…Immunohistochemical staining for CD34 is used to evaluate microvessel density (MVD) in numerous tumor tissues, and intratumoral MVD is useful in predicting relapse or metastasis (22)(23)(24). The assessment of VEGF expression significantly correlates with MVD in different types of tumors (14,15,(17)(18)(19)25).…”