Study of microvessel density and the expression of the angiogenic factors VEGF, bFGF and the receptors Flt-1 and FLK-1 in benign, premalignant and malignant prostate tissues.

Abstract

PURPOSE: Vascular endothelial growth factor (VEGF) is an angiogenic factor that stimulates endothelial cell growth and enhances vascular permeability. VEGF exerts its action by binding to the specific cell surface receptors, fms-like tyrosine kinase 1 (Flt-1) and fetal liver kinase 1 (FLK/KDR). In tumor angiogenesis, Vascular endothelial growth factor stimulates endothelial cells to produce Basic fibroblastic growth factor (bFGF), which further enhances angiogenic activity. Very little information on the expression of VEGF, bFGF, and the receptors Flt-1 and FLK/KDR is available. Herein, we evaluate the expression of these angiogenic factors and receptors in normal prostate, high grade prostate intraepithelial neoplasia (HGPIN) and prostatic cancer (CaP). MATERIALS AND METHODS: 58 selected surgical specimens exhibiting areas of normal prostate, HGPIN, and CaP were evaluated for microvessel density, and for VEGF, bFGF, Flt-1 and FLK/KDR protein expression by immunohistochemistry. Results were correlated with pathological data. RESULTS: There was a statistically significant increase in the microvessel density and in the expression of the angiogenic factors VEGF, bFGF and the receptors FLK/KDR and Flt-1, in the premalignant and malignant tissues in comparison with normal prostatic glands. Microvessel density also correlated with higher Gleason grade, pathological stage and the expression of the receptors FLK/KDR and Flt-1. CONCLUSIONS: The "initiation switch" of angiogenesis was observed to be an early event consistent with the recruitment of new vasculature into high grade PIN lesions and it increased in the progression of prostatic cancer.