title: Development of an evidence-based approach to external quality assurance for breast cancer hormone receptor immunohistochemistry: comparison of reference values.
abstract: BACKGROUND
  External quality assurance and proficiency testing programs for breast cancer predictive biomarkers are based largely on traditional ad hoc design; at present there is no universal consensus on definition of a standard reference value for samples used in external quality assurance programs.
  
  
  OBJECTIVE
  To explore reference values for estrogen receptor and progesterone receptor immunohistochemistry in order to develop an evidence-based analytic platform for external quality assurance.
  
  
  METHODS
  There were 31 participating laboratories, 4 of which were previously designated as "expert" laboratories. Each participant tested a tissue microarray slide with 44 breast carcinomas for estrogen receptor and progesterone receptor and submitted it to the Canadian Immunohistochemistry Quality Control Program for analysis. Nuclear staining in 1% or more of the tumor cells was a positive score. Five methods for determining reference values were compared.
  
  
  RESULTS
  All reference values showed 100% agreement for estrogen receptor and progesterone receptor scores, when indeterminate results were excluded. Individual laboratory performance (agreement rates, test sensitivity, test specificity, positive predictive value, negative predictive value, and κ value) was very similar for all reference values. Identification of suboptimal performance by all methods was identical for 30 of 31 laboratories. Estrogen receptor assessment of 1 laboratory was discordant: agreement was less than 90% for 3 of 5 reference values and greater than 90% with the use of 2 other reference values.
  
  
  CONCLUSIONS
  Various reference values provide equivalent laboratory rating. In addition to descriptive feedback, our approach allows calculation of technical test sensitivity and specificity, positive and negative predictive values, agreement rates, and κ values to guide corrective actions.
authors: Department of Pathology, Memorial University of Newfoundland, St John's, Canada.
authors: Nikita
authors: N
authors: Makretsov
authors: C Blake
authors: CB
authors: Gilks
authors: Reza
authors: R
authors: Alaghehbandan
authors: John
authors: J
authors: Garratt
authors: Louise
authors: L
authors: Quenneville
authors: Joel
authors: J
authors: Mercer
authors: Dragana
authors: D
authors: Palavdzic
authors: Emina E
authors: EE
authors: Torlakovic
mesh_terms: D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism; D055317:Evidence-Based Practice; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards*; D011786:Quality Control; D011960:Receptors, Estrogen / Q000032:analysis* / Q000378:metabolism; D011980:Receptors, Progesterone / Q000032:analysis* / Q000378:metabolism; D012016:Reference Values; D012680:Sensitivity and Specificity
chemical_list: D011960:Receptors, Estrogen; D011980:Receptors, Progesterone