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ER-α36, a novel isoform of ER-α66, is commonly over-expressed in apocrine and adenoid cystic carcinomas of the breast
  1. Semir Vranic1,2,
  2. Zoran Gatalica1,
  3. Hao Deng3,
  4. Snjezana Frkovic-Grazio4,
  5. Lisa M J Lee1,5,
  6. Olga Gurjeva6,
  7. Zhao-Yi Wang7
  1. 1Department of Pathology, Creighton University Medical Center, Omaha, Nebraska, USA
  2. 2Department of Pathology, Clinical Center of the University of Sarajevo, Sarajevo, Bosnia and Herzegovina
  3. 3Department of Pathology and Pathophysiology, School of Medicine, Jianghan University, Wuhan, China
  4. 4Department of Pathology, Institute of Oncology, Ljubljana, Slovenia
  5. 5Division of Anatomy, College of Medicine, The Ohio State University, Columbus, Ohio, USA
  6. 6Emergency Cardiology Department, Ukrainian Strazhesko Institute of Cardiology, Kiev, Ukraine
  7. 7Department of Medical Microbiology and Immunology, Creighton University Medical School, Omaha, Nebraska, USA
  1. Correspondence to Semir Vranic, Department of Pathology, Clinical Center of the University of Sarajevo, BA-71000 Sarajevo, Bosnia and Herzegovina; semir.vranic{at}


Background ER-α36 is a novel 36 kDa isoform of the full-length oestrogen receptor alpha (ER-α66). ER-α36 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-α36 in apocrine and adenoid cystic carcinoma of the breast, both of which are consistently ER-α66 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-α36 expression, along with expressions of ER-α66, progesterone receptor (PR) and androgen receptor (AR) using immunohistochemical methods.

Results All pure apocrine carcinomas showed a characteristic steroid receptor expression profile (ER-α66 and PR negative, AR strongly positive). ER-α36 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-α36. All adenoid cystic carcinomas were uniformly negative for all three classic steroid receptors, but ER-α36 was detected in 8/11 cases (72.7%, 95% CI 42.8 to 90) with the similar sub-cellular pattern of expression as in the pure apocrine carcinomas. When positive, adenoid cystic carcinomas expressed ER-α36 in the majority of cells (average 76%).

Conclusion ER-α36, a novel isoform of ER-α66, 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.

  • Breast cancer
  • ER-α36
  • adenoid cystic carcinoma
  • apocrine carcinoma
  • breast
  • breast pathology
  • immunohistochemistry
  • steroid receptors

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  • Preliminary results were in part presented at the 97th Annual Meeting of the United States and Canadian Academy of Pathology, Denver, Colorado, USA in March 2008, and the 31st Annual San Antonio Breast Cancer Symposium, in December 2008.

  • Funding SV was a research fellow at Creighton University Medical Center, Omaha, Nebraska, USA, and had been supported by a UICC American Cancer Society Beginning Investigators Fellowship (ACSBI) (ACS/08/004) funded by the American Cancer Society.

  • Competing interests None declared.

  • Ethics approval This study was conducted with the approval of the Institutional Review Board of Creighton University School of Medicine.

  • Provenance and peer review Not commissioned; externally peer reviewed.