ER-alpha 36, a novel isoform of ER-alpha 66, is commonly over-expressed in apocrine and adenoid cystic carcinomas of the breast

Background ER-alpha 36 is a novel 36 kDa isoform of the full-length oestrogen receptor alpha (ER-alpha 66). ER-alpha 36 primarily localises to the cytoplasm and the plasma membrane, and responds to membrane-initiated oestrogen and antioestrogen signalling pathways. Aim To examine the expression of ER-alpha 36 in apocrine and adenoid cystic carcinoma of the breast, both of which are consistently ER-alpha 36 negative and currently lack effective targeted therapeutic options. Methods 19 pure apocrine carcinomas (17 invasive and two in-situ carcinomas) and 11 adenoid cystic carcinomas of the breast were evaluated for ER-alpha 36 expression, along with expressions of ER-alpha 36, progesterone receptor (PR) and androgen receptor (AR) using immunohistochemical methods. Results All pure apocrine carcinomas showed a characteristic steroid receptor expression profile (ER-alpha 36 and PR negative, AR strongly positive). ER-alpha 36 expression was detected in 18/19 pure apocrine carcinomas (94.7%, 95% CI 75.1 to 98.7) in predominantly membranous and cytoplasmic distribution. When positive, pure apocrine carcinomas uniformly (100% of cells) expressed ER-alpha 36. All adenoid cystic carcinomas were uniformly negative for all three classic steroid receptors, but ER-alpha 36 was detected in 8/11 cases (72.7%, 95% CI 42.8 to 90) with the similar subcellular pattern of expression as in the pure apocrine carcinomas. When positive, adenoid cystic carcinomas expressed ER-alpha 36 in the majority of cells (average 76%). Conclusion ER-alpha 36 , a novel isoform of ER-alpha 36, is frequently over-expressed in apocrine and adenoid cystic carcinomas of the breast. These results indicate a potential for a novel targeted treatment in these cancers.