Digital image analysis of proliferative index: Two distinct populations of high-grade prostatic intraepithelial neoplasia in close proximity to adenocarcinoma of the prostate

A considerable amount of data has been collected showing the association of high-grade prostatic intraepithelial neoplasia (HGPIN) with adenocarcinoma of the prostate, and many studies have yielded results that suggest that HGPIN is a precursor of carcinoma. A few studies have indicated that HGPIN may, in some cases, be a sequela of prostatic adenocarcinoma. We examined the proliferative indices of HGPIN, carcinoma, and benign prostatic epithelium by computeraided counting of Ki-67-positive nuclei in 15 cases in which HGPIN and carcinoma were in close proximity. There were 13 radical prostatectomy specimens with prostate cancer and two cystoprostatectomy specimens with both transitional cell carcinoma and prostatic adenocarcinoma. First, we showed the accuracy of the computer-aided counting method compared with direct counting through the binoculars of the microscope. Then proliferative activity was assessed for each case by picking the two areas of carcinoma, the two areas of HGPIN, and the one area of benign epithelium with the greatest density of carcinomatous, dysplastic, and benign Ki-67-positive nuclei, respectively. The total number of nuclei and the number of positive nuclei were counted. Basal cells were not counted. The mean proliferative index was higher for cancer (caindex, average 0.054) than for HGPIN (pinindex, average 0.048) ( P