Vascular Endothelial Growth Factor (VEGF) and Microvessel Density in Squamous Cell Carcinomas of the Larynx: an Immunohistochemical Study

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Abstract
The distribution of vascular endothelial growth factor (VEGF), one of the most important angiogenic factors, and microvessel density (MVD) were assessed in laryngeal carcinomas by means of immunohistochemistry. Correlation of VEGF with MVD and clinical parameters (T stage, N stage, histological grading, survival, recurrence-free interval) was also examined. VEGF expression was evaluated semi-quantitatively and was observed in varying intensity (i) in tumour cells, (ii) in the stromal department as diffuse, sometimes strong reactivity, especially in close proximity to tumour masses and (iii) in macrophages and endothelial cells. Normal epithelium presented no VEGF reactivity except in the immediate vicinity of tumour transformation. Forty percent of our specimens exhibited substantial VEGF reactivity, whereas 20% showed no staining in tumour cells and stroma. These results could be positively correlated with MVD. Moreover, high-graded carcinomas revealed higher VEGF expression, but there was no association of tumour stage or lymph node status with VEGF or MVD. There was a trend in the survival and recurrence analysis towards a higher risk of disease relapse and shorter survival time for patients with enhanced VEGF expression. Apart from tumour cells, macrophages seem to be a substantial source of VEGF in carcinomas. This observation supports the concept of a pivotal role of these cells in tumour defence--in our case, promoting tumour formation by contributing to neovascularization. VEGF was also found in the connective tissue, where it seems to be bound on collagens and probably builds a reservoir for rapid enzymatic mobilization.