title: Oestrogen receptors β1 and βcx have divergent roles in breast cancer survival and lymph node metastasis.
abstract: BACKGROUND
  The expression of oestrogen receptor (ER) α characterises a subset of breast cancers associated with good response to endocrine therapy. However, the clinical significance of the second ER, ERβ1, and its splice variant ERβcx is still unclear.
  
  
  METHODS
  We here report an assessment of ERα, ERβ1 and ERβcx by immunohistochemistry using quantitative digital image analysis of 340 primary tumours and corresponding sentinel lymph nodes.
  
  
  RESULTS
  No differences were seen in ER levels in primary tumours vs lymph node metastases. ERβ1 and ERβcx were equally distributed among age groups and tumour histological grades. Loss of ERβ1 in the primary tumour was strongly associated with poor survival. Its prognostic impact was particularly evident in young patients and in high-grade tumours. The worst outcome was seen in the tumours lacking both ERα and ERβ1. ERβcx expression in the primary tumour correlated with a higher risk of lymph node metastasis, and with poor survival when expressed in sentinel node lymphocytes.
  
  
  CONCLUSIONS
  Our study reveals highly significant although antagonising roles of ERβ1 and ERβcx in breast cancer. Consequently, we suggest that the histopathological assessment of ERβ1 is of value as a prognostic and potentially predictive biomarker.
authors.affiliation: 1] Department of Oncology and Pathology, Karolinska Institutet, 171 77 Stockholm, Sweden [2] Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 14183 Huddinge, Sweden.
authors.forename: G
authors.initials: G
authors.lastname: Rosin
authors.affiliation: 1] Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 77 Stockholm, Sweden [2] Department of Breast and Endocrine Surgery, Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: de Boniface
authors.affiliation: Department of Oncology and Pathology, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: G M
authors.initials: GM
authors.lastname: Karthik
authors.affiliation: 1] Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 77 Stockholm, Sweden [2] Department of Breast and Endocrine Surgery, Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Frisell
authors.affiliation: 1] Department of Oncology and Pathology, Karolinska Institutet, 171 77 Stockholm, Sweden [2] Radiumhemmet, Karolinska Oncology, Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Bergh
authors.affiliation: 1] Department of Oncology and Pathology, Karolinska Institutet, 171 77 Stockholm, Sweden [2] Department of Clinical Pathology, Karolinska University Hospital, 171 76 Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Hartman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D047629:Estrogen Receptor beta / Q000378:metabolism*; D005260:Female; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000473:pathology*; D008875:Middle Aged; D011379:Prognosis; D055815:Young Adult
chemical_list: D047629:Estrogen Receptor beta