title: Solving the dilemma of the immunohistochemical and other methods used for scoring estrogen receptor and progesterone receptor in patients with invasive breast carcinoma.
abstract: BACKGROUND
  The authors attempted to resolve the dilemma posed by the lack of unanimity concerning the optimal immunohistochemical (IHC) method for determining and scoring estrogen receptor (ER) and progesterone receptor (PR).
  
  
  METHODS
  Sections for IHC were prepared from paraffin embedded tumor samples from 402 patients with lymph node positive breast carcinoma who had biochemical receptor values (obtained with the dextran-coated charcoal [DCC] method) and who were enrolled in a prospective, randomized trial (National Surgical Adjuvant Breast and Bowel Project protocol B-09). IHC receptors were scored independently by two observers according to percent, intensity, and any-or-none algorithms. Results from these evaluations and from two computer-assisted evaluations, DCC, and common pathologic characteristics were analyzed for optimum splits for positive reactions in univariate and multivariate analyses using a tree-structured model. Concordance, sensitivity, and specificity were determined between the DCC method and all other methods.
  
  
  RESULTS
  Interobserver agreement and concordance between the DCC method and the other methods and among the methods were high. Univariate analyses revealed that a positive ER score obtained with all methods was related significantly to overall survival (OS) at 5 years and at 10 years. Results related to PR scores and disease-free survival and recurrence-free survival were less consistent. In multivariate analysis, it also was found that all methods for scoring ER predicted a better prognosis for OS in patients with an unfavorable lymph node status at 5 years and 10 years. Patients in a favorable lymph node status group were discriminated further by nuclear grade.
  
  
  CONCLUSIONS
  All IHC methods for scoring ER appeared valid as prognostic indicators of OS in patients with positive lymph nodes. The any-or-none IHC method, by virtue of its simplicity, represents an appropriate choice for practical use.
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project Pathology Center and Allegheny General Hospital, West Penn Allegheny Health System, Pittsburgh, Pennsylvania 15212, USA. cgriffit@wpahs.org
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Fisher
authors.forename: Stewart
authors.initials: S
authors.lastname: Anderson
authors.forename: Scott
authors.initials: S
authors.lastname: Dean
authors.forename: David
authors.initials: D
authors.lastname: Dabbs
authors.forename: Bernard
authors.initials: B
authors.lastname: Fisher
authors.forename: Richard
authors.initials: R
authors.lastname: Siderits
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Pritchard
authors.forename: Telma
authors.initials: T
authors.lastname: Pereira
authors.forename: Charles
authors.initials: C
authors.lastname: Geyer
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D002606:Charcoal; D003911:Dextrans; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods*; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D015588:Observer Variation; D011379:Prognosis; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D012680:Sensitivity and Specificity; D013048:Specimen Handling
chemical_list: D003911:Dextrans; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D002606:Charcoal