Estrogen receptor β2 is inversely correlated with Ki-67 in hyperplastic and noninvasive neoplastic breast lesions

The purpose of the study is to compare expression levels of ΕRα, ERβ1, ERβ2 and cell proliferation marker Ki-67 in normal breast and hyperplastic and noninvasive neoplastic breast lesions.

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, ERβ1 and ERβ2 were evaluated using immunohistochemistry and correlated with Ki-67 labeling index (Ki-67 LI) and menopausal status of the patients.

Compared with normal breast, ERα expression increased in low to intermediate-grade DCIS (DCIS1/2) and tended to decrease in high-grade DCIS, while ERβ1 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 ERβ2 expression in the whole set of cases and with high ERα expression and low ERβ2 expression in the postmenopausal cases of the subset that is generated by excluding AM and high-grade DCIS. Postmenopausal status correlated with low ERβ1 expression in the whole set and with higher than normal Ki-67 LI, high ERα expression and low ERβ1 expression in the subset.

These findings are in accordance with an ERα-opposing oncosuppressive role of ERβ2 in mammary carcinogenesis along the HUT-AH-DCIS1/2 pathway.