Objectives: To examine estrogen receptor-beta (ERbeta) 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 ERbeta, with decreased expression of ERbeta accompanying CaP progression. It has been proposed that ERbeta 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.
Methods: The anti-ERbeta antibody GC17 was used in immunohistochemistry to characterize the expression of ERbeta in CaP metastasis specimens (n = 60) obtained from 20 patients who had died of CaP. Statistical analyses were performed to evaluate the association of ERbeta expression with clinical parameters, including prostate-specific antigen levels, radiotherapy, and estrogen exposure.
Results: Nuclear ERbeta 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 ERbeta staining and estrogen exposure (P = 0.05) was detected.
Conclusions: Our data have shown that ERbeta is expressed in CaP metastases, validating the initiation of studies to evaluate selective ER modulators for treatment of advanced CaP.