Differential expression of the estrogen receptor beta (ERβ) in human prostate tissue, premalignant changes, and in primary, metastatic, and recurrent prostatic adenocarcinoma

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Abstract
BACKGROUND Estrogen signaling mediated by the estrogen receptor beta (ERβ) has potential implications in normal and abnormal prostate growth. Few studies have addressed this issue in human prostate tissue leaving conflicting results on the immunolocalization of the ERβ in benign and neoplastic lesions. METHODS Using a new monoclonal antibody, the current study reports on the differential expression of the ERβ in tissue sections from 132 patients with prostate cancer. RESULTS The prostatic epithelium expressed the ERβ extensively in secretory luminal cell types and at lower levels in basal cells. Atrophic changes of the peripheral zone (PZ) were more immunoreactive than hyperplastic lesions of the transition zone (TZ). When compared with glandular tissue of the PZ, high-grade prostatic intraepithelial neoplasia (HGPIN) revealed decreased levels of the ERβ in 30 of 47 cases and was unreactive in six lesions. In informative cases with suitable internal controls, all primary tumors (n = 60), lymph node (n = 7), and bone metastases (n = 5) expressed the ERβ at variable degree. No correlation was found between the ERβ status, the primary Gleason grade (P = 0.254), and the pathological stage (P = 0.157). Recurrent adenocarcinoma revealed markedly decreased levels in 15 of 40 cases and was ERβ negative in five recurrent lesions. CONCLUSIONS The secretory epithelium is a major target of ERβ-mediated estrogen signaling in the human prostate. Its downregulation in HGPIN is consistent with chemopreventive effects that the ERβ may exert on the prostatic epithelium. The continuous expression of the receptor protein at significant levels in untreated primary and metastatic adenocarcinoma indicates that these tumors can use estrogens through an ERβ-mediated pathway. The partial loss of the ERβ in recurrent tumors after androgen-deprivation may reflect the androgen-dependence of ERβ gene expression in human prostate cancer. Prostate 54: 79–87, 2003.