Apoptotic index as a biomarker in prostatic intraepithelial neoplasia (PIN) and prostate cancer

Chemoprevention trials in prostate cancer would involve excessively long follow-up if conventional endpoints of efficacy are used. Prostatic intraepithelial neoplasia (PIN) may be an appropriate surrogate endpoint for monitoring outcome during prostate cancer chemoprevention studies. To address the question of whether PIN could be stratified into "stable" PIN and PIN likely to progress to invasive cancer, we selected patients with a single focus of peripheral zone cancer with ipsilateral and contralateral high-grade PIN. Sixteen patients met these criteria from a series of 550 patients treated by radical prostatectomy. We examined the rate of apoptosis in PIN and prostate cancer tissues by quantifying the number of apoptotic bodies per hundred cells (apoptotic index) on hematoxylin and eosin stained histological sections. Significant differences (ANOVA: p < 0.05) were detected between foci of prostatic intraepithelial neoplasia contralateral to the cancer and the cancer itself. There was no difference in the apoptotic index between a given cancer and a focus of PIN ipsilateral to the tumor in the same section. However, the range of apoptotic indices overlapped in all categories. Apoptotic indices appear to parallel the biological activity of PIN and malignant prostatic tissue, but may be of little benefit when used alone in monitoring the outcome of chemopreventive therapy in an individual patient.