Vascular endothelial growth factor expression and capillary architecture in high-grade PIN and prostate cancer in untreated and androgen-ablated patients

BACKGROUND. Recent studies have demonstrated that angiogenesis is a potent prognostic indicator for patients with prostate cancer (PCa) and have point ed out that the evaluation of vascular endothelial growth factor (VECF) is useful in assessing the angiogenic phenotype in PCa. The aim of the study w as to investigate immunohistochemically the expression of VEGF and its corr elation with the pattern of capillary architecture in prostate cancer and h igh-grade prostatic intraepithelial neoplasia (PIN), in untreated and andro gen-ablated patients. METHODS. forty-five patients who underwent radical prostatectomy (RP) for l ocalized prostate carcinoma were recruited for this study. The study popula tion included two groups: 35 patients who did not receive chemo-, hormone, or radiation therapy before surgery, and 10 patients who were under complet e androgen blockade (CAB) for 3 months at time of surgery. VEGF was examine d by immunohistochemistry, and its tissue expression was compared with the pattern of capillary architecture evaluated by immunostaining the endotheli al antigen CD34. The relationship of VEGF expression to chromogranin A-posi tive (e.g., neuroendocrine) cells was investigated. RESULTS. In normal tissue, the intensity of the VEGF immunoreactivity in th e cytoplasm of secretory cells ranged from negative to low. Very few basal cells stained for VEGF. All prostate cancer specimens stained positively, t he intensity of the immunoreaction ranging from low to strong and being cor related with the Gleason score. Strongly positive VEGF immunoreactivity was detected in vascular endothelial cells and in stromal cells surrounding bl ood vessels. Two discrete immunostaining patterns were observed in high-gra de PIN. VEGF expression of low-to-moderate intensity was defined as pattern A. The other, characterized by a strong cytoplasmic immunoreaction similar to that of poorly differentiated tumors, was defined as pattern B. The cap illary architecture in high-grade PIN with pattern A was similar to the ord erly vascular network seen in normal prostates, whereas in the pattern B it had the characteristics of microvessels usually seen in PCa. The degree of vascularization in the stroma adjacent to intensely VEGF-stained cells (ne uroendocrine phenotype) was higher than that noted in association with secr etory cells. CAB before surgery downregulated the expression of VEGF and de creased the degree of vascularization, except in the cell areas with neuroe ndocrine (NE) features. CONCLUSIONS. Our immunohistochemical results indicate that significant leve ls of VEGF are present in prostate cancer and in a population of PIN lesion s, expression being highest in association with NE cells. VEGF expression i s downregulated by hormonal manipulation, except in the population of NE ce lls. (C) 2000 Wiley-Liss, Inc.