title: Interobserver concordance in implementing the 2010 ASCO/CAP recommendations for reporting ER in breast carcinomas: a demonstration of the difficulties of consistently reporting low levels of ER expression by manual quantification.
abstract: OBJECTIVE
  Endocrine therapy reduces recurrence risk by 30% to 50% in estrogen receptor (ER)-positive breast cancer. The ER-positive threshold recommended by the American Society of Clinical Oncology/College of American Pathologists is 1% based on studies using the ER-6F11 antibody. ER-SP1 antibody has a higher sensitivity and is more widely used.
  
  
  METHODS
  We report interobserver concordance manually measuring ER in 264 breast cancers using ER-SP1 and 1D5 and 2 scoring methods (H-score and Allred score).
  
  
  RESULTS
  With both antibodies, 3% to 4% of cases have a low level of ER expression (1%-10%), more than previously reported (<1%). We find a high level of paired observer concordance with both antibodies and scoring methods (κ = 0.892-0.943) with no significant difference with method of scoring. Despite excellent concordance, positive/negative discordance was almost 5% among 3 observers using either antibody, an underappreciated clinically significant rate.
  
  
  CONCLUSIONS
  Discordance overwhelmingly reflected differing opinions recording the proportion of tumor cells positive with low levels of expression (<10% staining; 12/13 cases).
authors.affiliation: Dept of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, MCN C-3321, 1161 21st Ave S, Nashville, TN 37232;Emily.s.reisenbichler@vanderbilt.edu.
authors.forename: Emily S
authors.initials: ES
authors.lastname: Reisenbichler
authors.forename: Susan C
authors.initials: SC
authors.lastname: Lester
authors.forename: Andrea L
authors.initials: AL
authors.lastname: Richardson
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Dillon
authors.forename: Amy
authors.initials: A
authors.lastname: Ly
authors.forename: Jane E
authors.initials: JE
authors.lastname: Brock
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000175:diagnosis* / Q000378:metabolism; D019411:Clinical Laboratory Techniques / Q000379:methods / Q000592:standards; D005260:Female; D019983:Guideline Adherence; D006801:Humans; D015588:Observer Variation; D017410:Practice Guidelines as Topic; D011960:Receptors, Estrogen / Q000378:metabolism*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D012955:Societies, Medical; D014481:United States
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen
keywords: Breast carcinoma; Concordance; Estrogen receptor; Immunohistochemistry