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

Abstract

BACKGROUNDThe 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).METHODSSections 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.RESULTSInterobserver 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.CONCLUSIONSAll 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. Cancer 2005. © 2004 American Cancer Society.

Estrogen Receptor and Progesterone Receptor Status in Breast Cancer in Relation to Age, Histological Grade, Size of Lesion and Lymph Node Involvement

“…Recently, a refined assessment of hormone receptors in breast carcinoma has become necessary to select therapeutic agents according to the recommendations and guidelines for postoperative adjuvant systemic therapy of early breast cancer proposed by the International Consensus Panel during the St Gallen Conference in 2005 (Goldhirsch et al, 2005). The guidelines proposed 3 disease responsiveness categories: endocrine responsive, endocrine response uncertain, and endocrine nonresponsiveAs to the method for the detection and quantification of estrogen receptor (ER) and progesterone receptor (PR), immunohistochemical methods have been preferred because of their relative simplicity, low cost, speed of performance, application to small samples, precise identification of reactive elements, simple methods of fixation and storage, ability to be applied to archival material (Fisher et al, 2005), and better ability to predict response to adjuvant endocrine therapy owing to validation studies for ER (Harvey et al, 1999) and PR (Mohsin et al, 2004).…”

Immunohistochemistry compared to cytosol assays for determination of estrogen receptor and prediction of the long-term effect of adjuvant tamoxifen

“…Two retrospective adjuvant studies conducted on archival tissue, one by Ferno et al [30] on 98 patients which received adjuvant tamoxifen, the other reported by Harvey et al [31]showed that estrogen receptor positivity determined by IHC significantly predicted improved disease free survival in patients receiving adjuvant tamoxifen therapy. To our knowledge only three other studies [17][18][19] used randomized clinical trial populations receiving adjuvant therapy but the cohort of patients were smaller, had shorter duration of follow up and mixed treatment arms [17,18]. Regan at al re-evaluated and reported results from International Breast Cancer Study Group (IBCSG) trial VIII (pre-and perimenopausal patients) and trial IX (postmenopausal patients).…”

“…Immunohistochemistry and cytosol assays were shown to yield similar predictive and prognostic information [15][16][17], but the majority of these studies had a short follow-up and many patients received a range of therapies.…”

“…To our knowledge there are only few studies comparing these methods in an adjuvant randomized setting [17][18][19].…”

Diagnostic and Prognostic Importance of the Neutrophil Lymphocyte Ratio in Breast Cancer

“…While ER and PR scores were assessed; only nuclear expression was concerned (Lester et al, 2009;Hammond et al, 2010) and for ER staining of >10% of tumor nuclei was considered positive. PR expression was considered to be positive if the nuclei of more than 1% of cells were stained positive (Diaz et al, 2004;Fisher et al, 2005). HER2 score assessment was made according to intensities and the proportions of the cells which showed membrane staining (Lester et al, 2009;Gutierrez and Schiff, 2011).…”