Predictors of pathologic stage in prostatic carcinoma. The role of neovascularity

Abstract

Background. Prostate adenocarcinoma is a significant cause of morbidity and mortality in older men. However, the histologic prevalence far exceeds clinically manifest disease. Increased screening has resulted in the detection of a large number of carcinomas of unknown malignant potential. The authors investigated tumor angiogenesis to predict pathologic stage in prostatic tumors. Angiogenesis in prostatic intraepithelial neoplasia (PIN), a putative premalignant lesion, also was investigated. Methods. Immunohistochemistry was used to highlight the tumor vasculature. Vessels were quantified using computerized image analysis. A minimum of five randomly selected microscopic fields were measured from each tumor. To investigate PIN, the authors measured vessels per millimeter of gland perimeter, compared with benign glands in the same patient. Results. Vessel density (vessels per millimeter squared [vv/mm²]) correlated with pathologic stage. The mean vessel density of organ-confined tumors was 80.2 vv/mm² (95% confidence interval [CI], 71.4–91.0), compared with 110.4 vv/mm² (95% CI, 97.9–122.8) for tumors with capsular penetration or positive lymph nodes. Logistic regression analysis and modeling showed vessel density superior to histologic grade and preoperative prostate-specific antigen (PSA) level in distinguishing organ-confined tumors from those having extracapsular extension or pelvic lymph node metastasis. PIN in acini and ductules had increased microvascularity relative to benign epithelium in 18 of 25 tumors (P < 0.05). Conclusions. Neovascularity has been demonstrated to be a prerequisite for tumor progression. These data demonstrate that microvessel density in prostatic carcinoma is an independent predictor of pathologic stage and, presumably, malignant potential. Quantification of tumor angiogenesis may allow stratification of patients to type of treatment and may allow selection of expectant management for men with low tumor microvessel density.