Androgen receptor expression in prostatic intraepithelial neoplasia and cancer

Purpose: Androgen receptors are present in virtually all epithelial cells o f the prostate, including benign epithelium, high grade prostatic intraepit helial neoplasia and cancer. However, there have been variable results rega rding the clinical significance of cells expressing androgen receptors in p rostate cancer. We evaluated the predictive accuracy of androgen receptor e xpression in prostatic intraepithelial neoplasia and cancer for clinical pr ogression and survival in patients with organ confined prostate cancer trea ted with radical prostatectomy. Materials and Methods: The study consisted of 172 previously untreated pati ents who underwent radical prostatectomy at our clinic between 1987 and 199 1 with intermediate to high grade (Gleason score 6 to 9), pathological stag e T2 cancer and negative surgical margins. Mean followup was 7.4 years (ran ge 1.2 to 10.1). Mouse monoclonal anti-human androgen receptor antibody was used for immunohistochemical studies on select tissue sections from each c ase. We counted 100 nuclei from 3 separate areas of benign epithelium, pros tatic intraepithelial neoplasia and cancer (total 300 nuclei for each diagn ostic category) for each case. Mean nuclear androgen receptor expression wa s determined from the mean of the individual cases for each diagnostic cate gory. Intensity was also evaluated using a subjective scale from 0 (no stai ning) to 3 (strong staining). We determined the correlation of clinical pro gression and the number of androgen receptor immunoreactive prostatic intra epithelial neoplasia or cancer nuclei, and then performed multivariate anal ysis which included deoxyribonucleic acid ploidy, radical prostatectomy Gle ason score and preoperative serum prostate specific antigen using the Cox p roportional hazards model. Progression was defined as a positive biopsy, po sitive bone scan or biochemical progression (postoperative serum prostate s pecific antigen greater than 0.2 ng./ml.). Results: Nuclear immunoreactivity for androgen receptors was observed in al l cases. Mean percent of immunoreactive nuclei was higher in benign epithel ium than in prostatic intraepithelial neoplasia and cancer (56.3, 46.1 and 53.6%, respectively, pairwise comparisons p < 0.05 for each pair). With rar e exceptions, basal cells in benign epithelium and prostatic intraepithelia l neoplasia were negative. The most intense nuclear staining was observed i n benign epithelium. Immunoreactivity was also faint but detectable in the cytoplasm in prostatic intraepithelial neoplasia but not in benign epitheli um or cancer. Mean number of androgen receptor immunoreactive nuclei in pro static intraepithelial neoplasia and cancer was not a significant univariat e or multivariate predictor of clinical and/or biochemical progression, or all cause survival (all p > 0.05). Conclusions: Androgen receptor expression was present in all cases of benig n epithelium, prostatic intraepithelial neoplasia and cancer. The greatest extent and intensity of expression were observed in benign epithelium, with about half of the nuclei showing intense immunoreactivity. The number of a ndrogen receptor immunoreactive nuclei in prostatic intraepithelial neoplas ia and cancer in patients with organ confined prostate cancer treated with radical prostatectomy was not predictive of progression or survival.