Elevated estrogen receptor expression in human prostatic stromal cells by androgen ablation therapy

Purpose: The presence of estrogen receptors (ER) in human prostatic tissue is a longstanding, controversial issue. In a few experimental animal models androgen deprivation was shown to be associated with a spontaneous increased ER expression in prostatic tissue. We intended to study whether these observations also apply to human prostatic tissue. Materials and Methods: Estrogen receptor expression by stromal and glandular cells was studied by immunohistochemistry in prostatectomy specimens of 21 patients with prostate cancer, treated for 3 months with a luteinizing hormone-releasing hormone (LHRH) agonist and flutamide. In addition 2 patients treated with estrogens were also examined. For comparison, ER expression was also studied in a series of 18 prostatectomy specimens of untreated patients. Results: The specimens of patients treated with androgen blockade showed atrophic changes of the gland as well as basal cell hyperplasia, features characteristic for this therapy. Although stromal cells of prostatectomy specimens from untreated patients were largely ER negative, those of patients exposed to androgen ablation therapy or estrogen therapy had an intense nuclear ER expression in a great number of stromal cells around prostatic glands. Sporadic epithelial cells lining the glands displayed some nuclear ER expression. Prostatic glands from treated patients with basal cell hyperplasia lacked ER expression. In all treated and untreated cases the carcinoma cells were ER negative. Conclusions: Androgen deprivation leads to an upregulation of stromal ER expression in human prostate. Estrogen-induced morphological epithelial changes could be explained by a paracrine interaction between stromal and epithelial cells.