Expression of Estrogen Receptor-Beta and Its Isoforms in Breast Cancers
Y Choi. Yale School of Medicine, Bridgeport
Background: ER- has several isoforms and some of them have shown to be associated with unfavorable outcomes. Previously, our study showed ER- wild type (wt) expression in ER- negative tumors. This study aims to test expression of ER- wt and its isoforms in triple negative (TN) and tamoxifen resistant (TR) breast cancers.
Design: A tissue microarray sldies from 226 breast cancers were tested for the expression of ER- (Dako. CA), PR (Dako, CA), HerceptTest kit (Dako, CA), ER- wt (Biogenex, CA), ER-1(Dako, CA), ER-2/bcx(AbD serotec, UK), ER-,CT(Lake Placid, NY), ER-beta NT(Millipore, MA) and ER-1(AbD serotec,UK) using standard immunohistochemistry procedures. They were also analyzed for histopathology and associations between ER- andp53 and Ki-67. More than10% nuclear reaction was considered positive.
Results: The 226 breast cancers consisted of 20 stage 0 cases (9%), 20 stage I cases (9%), 63 stage II cases (28%), 23 stage III cases (10%), and 100 stage IV cases (44%) which included 63 patients who were treated with tamoxifen but developed stage IV disease. ER- negative and TN cancers comprised of 55.4% (124/226) and 20.8% (47/226), respectively. TN cancers consisted of grade 3 in 74.5%(35/47), ductal type in 59.6% (28/47), basaloid in 5.5% (12/47), apocrine type in 8.5% (4/47) and metaplastic changes in 2.1% (1/47).TN cancers showed expression of ER- wild (wt), ER-2/bcx, and ER-1 in 57.8% (26/45), 63.6% (28/44), and 64.4% (29/45), respectively and co-expression of all three ER- types in 51.2% (22/43) and no ER- expression in 2.3% (1/43).TR cases showed expression of ER- wt, ER-2/bcx and ER-1 in 50.8% (32/63), 49.1% (30/61), and 54.7% (33/61), respectively. P53 expression was present in 27.7% (13/47) of TN and 33.4 %( 21/62) of TR cases compared to 34.5% (78/226) of the total. Ki-67 expression was in 6.4% (3/47) of TN and 12.3% (8/62) of TR versus 18.1% (41/226) of total cases. Ki-67 co-expressed with ER-beta wt in 92.6% (38/41), with ER-1 in 97.6% (40/41), and with ER-2 in 95.1% (39/41) of TN and with ER- wt in 100% (8/8), ER-1 in 100% (8/8), and ER-2 in 62.5%(5/8) of TR.
Conclusions: ER-wt, ER-1 and ER-2/bcx are frequently expressed in TN and TR breast cancers. A significant correlation between expression of the three ER- types and Ki-67 expression suggests that both TN and TR have ER- positive proliferating cancer cell, not responding to the treatment. Both ER-1 and ER-2 expression were similar.Presence of ER- in this sub-population of breast cancers may have significant clinical and therapeutic implication, and ER- may be involved in estrogen signaling in these cancers.
Wednesday, March 11, 2009 9:30 AM
Poster Session V # 14, Wednesday Morning