Estrogen Receptor β

Context—A new class of estrogen receptors was discovered in 1996 and named estrogen receptor β (ER-B); the traditional estrogen receptor, which until a little more than 10 years ago was thought of as the only estrogen receptor in existence, is now called estrogen receptor α. Estrogen receptor β has at least 5 isoforms, which may have different functions and have different tissue distribution. The significance of ER-B expression in tumors was first demonstrated in breast cancer, with several studies demonstrating that women with ER-B–positive breast cancers treated with adjuvant tamoxifen have better survival, independent of estrogen receptor α expression. Pathologists need to be more aware of this increasingly important protein, as it will soon find its way into routine clinical practice. Objective—To provide pathologists with a concise review of ER-B, with special emphasis on current and potential clinical relevance. Data Sources—A search of the English literature in PubMed (National Library of Medicine, Bethesda, Maryland) for articles with titles including “estrogen receptor beta,” with emphasis on “immunohistochemistry.” Abstracts were reviewed, and selected articles were used as the basis for writing this review, mostly based on their relevance to pathology. Conclusions—Estrogen receptor β and its isoforms have wider tissue distribution, including the gastrointestinal tract, lung, and brain, than the traditional estrogen receptor, now called estrogen receptor α. Estrogen receptor β expression in breast cancer is associated with favorable outcome in women treated with adjuvant tamoxifen, even in tumors negative for estrogen receptor α. The clinical significance of ER-B expression in tumors other than breast is currently under investigation.