Comparison of estrogen receptor determinations by a biochemical ligand-binding assay and immunohistochemical staining with monoclonal antibody ER1D5 in females with lymph node positive breast carcinoma entered on two prospective clinical trials

Cancer. 1996 Aug 15;78(4):764-72. doi: 10.1002/(SICI)1097-0142(19960815)78:4<764::AID-CNCR12>3.0.CO;2-T.

Abstract

Background: The measurement of estrogen receptors (ER) in breast cancer specimens has traditionally been assessed with a dextran-coated charcoal assay (DCCA). More recently the immunohistochemical staining (IHC) method has gained increasing popularity because of its ability to use fixed tissue, assess needle biopsies, and reduce cost. Controversy exists over the accuracy of IHC compared with that of DCCA in determining ER. We compared these two techniques using tumor tissue obtained from a large group of females with lymph node positive breast carcinoma with long term follow-up.

Methods: Breast carcinoma tissue was obtained from a large group of females with node positive breast carcinoma participating in two adjuvant chemotherapy trials. ER was determined by the traditional DCCA method and by IHC using the ER1D5 antibody. Disease free survival (DFS) and overall survival (OS) were assessed by each of these methods.

Results: ER status was determined by DCCA and IHC in tumor tissue obtained from 316 females. A concordance of 79% was observed for the determination of ER-positive tumors. Of the discordant results, the majority of DCCA-negative, IHC-positive tumors could be explained by a low level of DCCA positivity (< 10 fmol) or IHC staining of nonmalignant cells. A much higher rate of discordant results was observed in premenopausal females. Of the DCCA-negative, IHC-positive patients 97% were premenopausal and of the DCCA-positive, IHC-negative patients 79% were premenopausal. ER by DCC appears to perform better than ER by IHC as a prognostic factor in terms of DFS and OS.

Conclusions: When compared with DCCA, IHC with monoclonal antibody ER1D5 appears to be a reasonable substitute for the determination of ER. Although DCCA appeared to perform better as a determinant of prognosis, ER detection is used primarily for deciding on hormonal therapy. Review of discordant cases indicates IHC may more accurately reflect the ER status of malignant cells in some patients. Attention must be paid to quality control considerations in performance of IHC staining.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / pathology
  • Adenocarcinoma / ultrastructure*
  • Adult
  • Aged
  • Antibodies, Monoclonal
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Breast Neoplasms / ultrastructure*
  • Charcoal
  • Chemotherapy, Adjuvant
  • Dextrans
  • Female
  • Humans
  • Immunohistochemistry
  • Ligands
  • Lymph Nodes / pathology
  • Lymphatic Metastasis
  • Middle Aged
  • Paraffin Embedding
  • Prospective Studies
  • Randomized Controlled Trials as Topic
  • Receptors, Estrogen / analysis*
  • Time Factors
  • Tissue Fixation

Substances

  • Antibodies, Monoclonal
  • Dextrans
  • Ligands
  • Receptors, Estrogen
  • Charcoal