Solving the dilemma of the immunohistochemical and other methods used for scoring estrogen receptor and progesterone receptor in patients with invasive breast carcinoma

Edwin R. Fisher, Stewart Anderson, Scott Dean, David Dabbs, Bernard Fisher, Richard Siderits, Jeffrey Pritchard, Telma Pereira, Charles Geyer, Norman Wolmark

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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.

Original languageEnglish (US)
Pages (from-to)164-173
Number of pages10
JournalCancer
Volume103
Issue number1
DOIs
StatePublished - Jan 1 2005

Fingerprint

Progesterone Receptors
Estrogen Receptors
Research Design
Breast Neoplasms
Charcoal
Dextrans
Lymph Nodes
Survival
Multivariate Analysis
Paraffin
Disease-Free Survival
Breast
Recurrence
Sensitivity and Specificity

Keywords

  • Breast carcinoma
  • Diagnostic methods
  • Immunohistochemical
  • Receptors

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Solving the dilemma of the immunohistochemical and other methods used for scoring estrogen receptor and progesterone receptor in patients with invasive breast carcinoma. / Fisher, Edwin R.; Anderson, Stewart; Dean, Scott; Dabbs, David; Fisher, Bernard; Siderits, Richard; Pritchard, Jeffrey; Pereira, Telma; Geyer, Charles; Wolmark, Norman.

In: Cancer, Vol. 103, No. 1, 01.01.2005, p. 164-173.

Research output: Contribution to journalArticle

Fisher, ER, Anderson, S, Dean, S, Dabbs, D, Fisher, B, Siderits, R, Pritchard, J, Pereira, T, Geyer, C & Wolmark, N 2005, 'Solving the dilemma of the immunohistochemical and other methods used for scoring estrogen receptor and progesterone receptor in patients with invasive breast carcinoma', Cancer, vol. 103, no. 1, pp. 164-173. https://doi.org/10.1002/cncr.20761
Fisher, Edwin R. ; Anderson, Stewart ; Dean, Scott ; Dabbs, David ; Fisher, Bernard ; Siderits, Richard ; Pritchard, Jeffrey ; Pereira, Telma ; Geyer, Charles ; Wolmark, Norman. / Solving the dilemma of the immunohistochemical and other methods used for scoring estrogen receptor and progesterone receptor in patients with invasive breast carcinoma. In: Cancer. 2005 ; Vol. 103, No. 1. pp. 164-173.
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AU - Anderson, Stewart

AU - Dean, Scott

AU - Dabbs, David

AU - Fisher, Bernard

AU - Siderits, Richard

AU - Pritchard, Jeffrey

AU - Pereira, Telma

AU - Geyer, Charles

AU - Wolmark, Norman

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N2 - 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.

AB - 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.

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