Estrogen receptor ß2 is inversely correlated with Ki-67 in hyperplastic and noninvasive neoplastic breast lesions.

PURPOSE: The purpose of the study is to compare expression levels of ΕRα, ERß1, ERß2 and cell proliferation marker Ki-67 in normal breast and hyperplastic and noninvasive neoplastic breast lesions. MATERIALS AND METHODS: Routinely processed breast tissue from 55 patients provided 65 cases of noninvasive lesions, namely, epithelial hyperplasia of usual type (HUT), apocrine metaplasia (AM), atypical hyperplasia (AH) and ductal carcinoma in situ (DCIS) and 14 cases of adjacent normal breast tissue. Expression of ERα, ERß1 and ERß2 were evaluated using immunohistochemistry and correlated with Ki-67 labeling index (Ki-67 LI) and menopausal status of the patients. RESULTS: Compared with normal breast, ERα expression increased in low to intermediate-grade DCIS (DCIS1/2) and tended to decrease in high-grade DCIS, while ERß1 expression decreased in DCIS irrespective of grade. Mean Ki-67 LI in HUT, low to intermediate-grade DCIS and high-grade DCIS was higher than in normal breast. Higher than normal Ki-67 LI correlated with low ERß2 expression in the whole set of cases and with high ERα expression and low ERß2 expression in the postmenopausal cases of the subset that is generated by excluding AM and high-grade DCIS. Postmenopausal status correlated with low ERß1 expression in the whole set and with higher than normal Ki-67 LI, high ERα expression and low ERß1 expression in the subset. CONCLUSIONS: These findings are in accordance with an ERα-opposing oncosuppressive role of ERß2 in mammary carcinogenesis along the HUT-AH-DCIS1/2 pathway.

Estrogen receptor beta 2 is associated with poor prognosis in estrogen receptor alpha-negative breast carcinoma.

PURPOSE: Our aim was to examine the prognostic significance of ERbeta1 and ERbeta2 expression in ERalpha-negative breast carcinomas. MATERIALS AND METHODS: We evaluated nuclear and cytoplasmic expression of ERbeta1 and ERbeta2 by immunohistochemistry in a group of 95 patients with long follow-up. ERbeta1 and ERbeta2 status was correlated with clinicopathological parameters and disease outcome. Univariate and multivariate analyses of ERbeta1 and ERbeta2 as independent markers of disease-free survival (DFS) were carried out using the Cox proportional hazards model. RESULTS: Nuclear ERbeta1 (nERbeta1) and nERbeta2 status was positively correlated (p = 0.01). nERbeta1 positivity was associated with low histological grade (p = 0.01) in all patients and in the nERbeta2-positive subgroup (p = 0.03) but not in the nERbeta2-negative (p = 0.27). nERbeta2 positivity was associated with lymph node involvement and tumor relapse in all cases (p < 0.00 and p < 0.00, respectively) and in the nERbeta1-negative subgroup (p < 0.00 and p < 0.00, respectively) but not in the nERbeta1-positive (p = 0.09 and p = 0.20, respectively). nERbeta2 positivity was associated with poor DFS in all patients (log-rank p <0.00), in the post-menopausal patient subgroup (log-rank p = 0.02) and in the HER2-negative (triple-negative) subgroup (log-rank p = 0.04). Cox multivariate analysis including ERbeta1, ERbeta2 and established clinicopathological variables highlighted ERbeta2 as an independent marker of early disease recurrence (hazard ratio 4.87; 95 % confidence interval 1.07-22.3; p = 0.04). CONCLUSION: High nERbeta2 is an independent marker of early relapse in ERalpha-negative breast carcinoma, and in particular, in the nERbeta1-negative, the post-menopausal patient and the triple-negative subgroups. These findings suggest that inhibition of expression and/or function of ERbeta2 could improve disease outcome.