Proliferative activity in benign and neoplastic prostatic epithelium

The increasing availability of means for the early detection of prostatic cancer has brought under scrutiny the criteria used for prognosis and emphasized our limitations in understanding what determines the rate of progression in these cancers. The rate of cancer cell proliferation has been under intense investigation, which, however, has yielded conflicting results. In this study we evaluated the proliferative activity of benign and neoplastic prostatic epithelium, using various existing methodologies. We first analysed the variability introduced by the methodological approach and then attempted to demonstrate whether determination of the proliferative capacity had any clinical consequence that complemented the histological grading. Tissue samples from patients, 88 with cancer and 46 with benign prostatic pathology, were studied using in vitro bromodeoxyuridine (BrdU) incorporation as well as Ki67 and the proliferating cell nuclear antigen (PCNA) to estimate the proliferative activity. Increased proliferation was found consistently in inflammation and metaplasia, but not in hyperplasia. In contrast, cancers showed marked variability. Although average proliferation indices increased with grade, there was a wide scatter of values. Correlation was stronger with stage, but also depended on the methodology. Bromodeoxyuridine indices over 10 per mille had a positive predictive value of 79 per cent for cancers extending beyond the prostatic capsule and may prove particularly helpful for evaluating patients with grade 7 cancer. This observation is significant, since grade 7 cancers are the most frequent and the least predictable.