Document Detail

Standardization of estrogen receptor measurement in breast cancer suggests false-negative results are a function of threshold intensity rather than percentage of positive cells.
MedLine Citation:
PMID:  21709197     Owner:  NLM     Status:  MEDLINE    
PURPOSE: Recent misclassification (false negative) incidents have raised awareness concerning limitations of immunohistochemistry (IHC) in assessment of estrogen receptor (ER) in breast cancer. Here we define a new method for standardization of ER measurement and then examine both change in percentage and threshold of intensity (immunoreactivity) to assess sources for test discordance.
METHODS: An assay was developed to quantify ER by using a control tissue microarray (TMA) and a series of cell lines in which ER immunoreactivity was analyzed by quantitative immunoblotting in parallel with the automated quantitative analysis (AQUA) method of quantitative immunofluorescence (QIF). The assay was used to assess the ER protein expression threshold in two independent retrospective cohorts from Yale and was compared with traditional methods.
RESULTS: Two methods of analysis showed that change in percentage of positive cells from 10% to 1% did not significantly affect the overall number of ER-positive patients. The standardized assay for ER on two Yale TMA cohorts showed that 67.9% and 82.5% of the patients were above the 2-pg/μg immunoreactivity threshold. We found 9.1% and 19.7% of the patients to be QIF-positive/IHC-negative, and 4.0% and 0.4% to be QIF-negative/IHC-positive for a total of 13.1% and 20.1% discrepant cases when compared with pathologists' judgment of threshold. Assessment of survival for both cohorts showed that patients who were QIF-positive/pathologist-negative had outcomes similar to those of patients who had positive results for both assays.
CONCLUSION: Assessment of intensity threshold by using a quantitative, standardized assay on two independent cohorts suggests discordance in the 10% to 20% range with current IHC methods, in which patients with discrepant results have prognostic outcomes similar to ER-positive patients with concordant results.
Allison W Welsh; Christopher B Moeder; Sudha Kumar; Peter Gershkovich; Elaine T Alarid; Malini Harigopal; Bruce G Haffty; David L Rimm
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-06-27
Journal Detail:
Title:  Journal of clinical oncology : official journal of the American Society of Clinical Oncology     Volume:  29     ISSN:  1527-7755     ISO Abbreviation:  J. Clin. Oncol.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-29     Completed Date:  2011-08-16     Revised Date:  2013-06-28    
Medline Journal Info:
Nlm Unique ID:  8309333     Medline TA:  J Clin Oncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2978-84     Citation Subset:  IM    
Department of Pathology, BML 116, Yale University School of Medicine, 310 Cedar St, PO Box 208023, New Haven, CT, USA.
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MeSH Terms
Breast Neoplasms / metabolism*
Carcinoma, Ductal, Breast / metabolism*
Cell Line, Tumor
False Negative Reactions
Fluorescent Antibody Technique
Gene Expression Regulation, Neoplastic
Receptors, Estrogen / metabolism*
Tumor Markers, Biological / metabolism*
Grant Support
Reg. No./Substance:
0/Receptors, Estrogen; 0/Tumor Markers, Biological

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