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 pointed out that the evaluation of vascular endothelial growth factor (VEGF) is useful in assessing the angiogenic phenotype in PCa. The aim of the study was to investigate immunohistochemically the expression of VEGF and its correlation with the pattern of capillary architecture in prostate cancer and high-grade prostatic intraepithelial neoplasia (PIN), in untreated and androgen-ablated patients.


METHODS
Forty-five patients who underwent radical prostatectomy (RP) for localized prostate carcinoma were recruited for this study. The study population included two groups: 35 patients who did not receive chemo-, hormone, or radiation therapy before surgery, and 10 patients who were under complete androgen blockade (CAB) for 3 months at time of surgery. VEGF was examined by immunohistochemistry, and its tissue expression was compared with the pattern of capillary architecture evaluated by immunostaining the endothelial antigen CD34. The relationship of VEGF expression to chromogranin A-positive (e.g., neuroendocrine) cells was investigated.


RESULTS
In normal tissue, the intensity of the VEGF immunoreactivity in the cytoplasm of secretory cells ranged from negative to low. Very few basal cells stained for VEGF. All prostate cancer specimens stained positively, the intensity of the immunoreaction ranging from low to strong and being correlated with the Gleason score. Strongly positive VEGF immunoreactivity was detected in vascular endothelial cells and in stromal cells surrounding blood vessels. Two discrete immunostaining patterns were observed in high-grade 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 capillary architecture in high-grade PIN with pattern A was similar to the orderly 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 (neuroendocrine phenotype) was higher than that noted in association with secretory cells. CAB before surgery downregulated the expression of VEGF and decreased the degree of vascularization, except in the cell areas with neuroendocrine (NE) features.


CONCLUSIONS
Our immunohistochemical results indicate that significant levels of VEGF are present in prostate cancer and in a population of PIN lesions, expression being highest in association with NE cells. VEGF expression is downregulated by hormonal manipulation, except in the population of NE cells.
Mazzucchelli
R
R
Institute of Pathological Anatomy and Histopathology, School of Medicine, University of Ancona, Italy.
Montironi
R
R
Santinelli
A
A
Lucarini
G
G
Pugnaloni
A
A
Biagini
G
G
D000230:Adenocarcinoma / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D000813:Anilides / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002196:Capillaries / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology; D016228:Endothelial Growth Factors / Q000096:biosynthesis*; D017273:Goserelin / Q000008:administration & dosage; D006801:Humans; D007150:Immunohistochemistry; D008222:Lymphokines / Q000096:biosynthesis*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000378:metabolism / Q000503:physiopathology*; D009570:Nitriles; D011468:Prostatectomy; D019048:Prostatic Intraepithelial Neoplasia / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000098:blood supply* / Q000188:drug therapy / Q000378:metabolism; D014105:Tosyl Compounds; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000726:Androgen Antagonists; D000813:Anilides; D016228:Endothelial Growth Factors; D008222:Lymphokines; D009570:Nitriles; D014105:Tosyl Compounds; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D017273:Goserelin; C053541:bicalutamide