To examine estrogen receptor-beta (ERβ) expression in prostate cancer (CaP) metastases, thereby providing a basis for conducting estrogen therapy studies in patients with metastatic CaP. Advanced androgen-independent CaP is a serious health problem with no effective treatment at present. Estrogens have been reported to inhibit the growth of CaP cells in androgen-free environments. Recent reports have shown that the prostatic epithelium and primary CaP cells express ERβ, with decreased expression of ERβ accompanying CaP progression. It has been proposed that ERβ may play a role in the growth regulation of prostate cells. The targeting of ERs by selective ER modulators might be an effective method of treating advanced CaP. The anti-ERβ antibody GC17 was used in immunohistochemistry to characterize the expression of ERβ in CaP metastasis specimens (n = 60) obtained from 20 patients who had died of CaP. Statistical analyses were performed to evaluate the association of ERβ expression with clinical parameters, including prostate-specific antigen levels, radiotherapy, and estrogen exposure. Nuclear ERβ staining was detected in all bone CaP metastases (33 of 33) and nonosseous CaP metastases (27 of 27). However, a large variability in the percentage of immunoreactive cells (5% to 100%) was found among patients, as well as among individual patient samples. A statistically significant negative association between nuclear ERβ staining and estrogen exposure (P = 0.05) was detected. Our data have shown that ERβ is expressed in CaP metastases, validating the initiation of studies to evaluate selective ER modulators for treatment of advanced CaP.
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