The diagnosis of well-differentiated adenocarcinoma of the prostate can be difficult on needle biopsy specimens. Nucleolar prominence has proven to be a useful diagnostic variable, but its objective evaluation has had limited study. To find nucleolar criteria that might differentiate benign from malignant conditions, we examined 41 open prostatectomy specimens, 25 of which were removed for well-differentiated adenocarcinoma and 16 of which were removed for benign prostatic hypertrophy (BPH). Four acini of carcinoma, prostatic intraepithelial neoplasia (PIN), atypical adenomatous hyperplasia (AAH), nodular hyperplasia, and normal tissue were examined. The total number of nuclei with nucleoli 3 microns or greater (N'), the fraction of nuclei with nucleoli 3 microns or greater (N'/N), and the average diameters of nucleoli 3 microns or greater (AVG) were recorded. Hyperplastic and normal areas, when compared with carcinoma, had significantly smaller N',N'/N, and AVG values (P less than 0.005). The N' and N'/N values were significantly higher in hyperplasia when compared with normal acini (P less than 0.005). In addition, N' and N'/N values in PIN were significantly greater than those in AAH (P less than 0.0001). In comparing prostates with and without carcinoma, N' and N'/N were significantly different for hyperplastic areas. In only two cancer areas and one PIN area was the N'/N ratio less than 0.31, which was the highest value for either hyperplastic or normal areas. Although AVG also were significantly different, they did not improve discrimination between the groups. We conclude that N'/N ratios are useful in diagnosing well-differentiated prostatic adenocarcinoma on small tissue samples.
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