Summary
Nine laboratories cooperating in the Receptor Study Group of the EORTC compared results of ligand binding assay supplemented with Scatchard plot analysis (LBA) and enzyme immunoassay (EIA) for the assessment of oestrogen receptors in 1665 breast cancer cytosols. An excellent agreement was observed between results of Scatchard plot analysis and EIA in each laboratory. Linear correlation coefficients of log-transformed data (log [(ER + 10)/10]) ranged from 0.839 to 0.977 (n = 52−373; P < 0.001); Spearman's R ranged from 0.797 to 0.972 (P < 0.001). Orthogonal regression analysis on log-transformed data revealed slopes of 0.794 to 1.141 and intercepts of − 0.057 to 0.154 corresponding to − 1.2 to 4.3 fmole/mg protein. Both assays compared equally well for pre- as well as postmenopausal patients, which confirms that occupied receptors are not extracted during the preparation of cytosol. The percentage discordance in the classification of tumours as ER positive or negative varied from 4.1 to 13.3 when a cut-off value of 10 fmol/mg protein was used, and from 1.4 to 7.5 at a cut-off level of 20. Considerable variations were observed in the actual receptor levels reported by each laboratory. Since these differences occurred in the results of both methods, they are attributed to differences in tissue handling. It is concluded that the ER-EIA is an excellent alternative to Scatchard plot analysis for the assay of oestrogen receptors. It is recommended, however, that laboratories performing assays on samples obtained from patients who are eligible for entrance in EORTC clinical trials and who wish to use the EIA should validate this assay against the Scatchard plot assay in their own setting.
References
EORTC Breast Cancer Cooperative Group: Standard for the assessment of hormone receptors in human breast cancer. Eur J Cancer 9: 379–381, 1973
EORTC Breast Cancer Cooperative Group: Revision of the standards for the assessment of hormone receptors in human breast cancer. Eur J Cancer 16: 1513–1515, 1980
Koenders A, Thorpe SM (on behalf of the EORTC Receptor Group): Standardization of steroid receptor assays in human breast cancer-I. Reproducibility of estradiol and progesterone receptor assays. Eur J Cancer Clin Oncol 19: 1221–1229, 1983
Koenders A, Thorpe SM (on behalf of the EORTC Receptor Group): Standardization of steroid receptor aasays in human breast cancer-II. Samples with low receptor content. Eur J Cancer Clin Oncol 19: 1467–1472, 1983
Thorpe SM, Koenders A (on behalf of the EORTC Receptor Group): Standardization of steroid receptor assays in human breast cancer-III. Selection of reference material for intra- and inter-laboratory quality control. Eur J Cancer Clin Oncol 22: 939–944, 1986
Koenders A, Thorpe SM (on behalf of the EORTC Receptor Group): Standardization of steroid receptor assays in human breast cancer-IV. Long-term within- and between-laboratory variation of estrogen and progesterone receptor assays. Eur J Cancer Clin Oncol 22: 945–952, 1986
Zava DT, Guelpa C: A quality control study to assess the intralaboratory variability of routine estrogen and progesterone receptor assays. Eur J Cancer Clin Oncol 18: 713–721, 1982
Ryan ED, Clark AF, Mobbs BG, Ooi TC, Sutherland DJA, Tustanoff ER: Inter-laboratory quality control of estrogen and progesterone receptor assays in breast cancer tissue using lyophilized cytosols. Clin Biochem 18: 20–26, 1985
Raam S, Gelman DR, Cohen JL: Estrogen receptor assays: Interlaboratory and intralaboratory variations in the measurement of receptors using the dextran-coated charcoal technique: a study sponsored by the E.C.O.G. Eur J Cancer Clin Oncol 17: 643–649, 1981
Borjesson BW, McGinley R, Foo TMS, Smyth C, Toppilla M, Compton P, Sarfaty GA: Estrogen and progesterone receptor assays in human breast cancer: sources of variation between laboratories. Eur J Cancer Clin Oncol 23: 999–1004, 1987
King WJ, Greene GL: Monoclonal antibodies localize oestrogen receptor in the nuclei of target cells. Nature 307: 745–747, 1984
King WJ, DeSombre ER, Jensen EV, Greene GL: Comparison of immunocytochemical and steroid-binding assays for estrogen receptor in human breast tumors. Cancer Res 45: 293–304, 1985
Leclercq G, Bojar H, Goussard J, Nicholson RI, Pichon M-F, Piffanelli A, Pousette A, Thorpe S, Lonsdorfer M: Abbott monoclonal enzyme immunoassay measurement of estrogen receptors in human breast cancer: a European multicenter study. Cancer Res (Suppl) 46: 4233s-4236s, 1986
Jordan VC, Jacobson HI, Keenan EJ: Determination of estrogen receptor in breast cancer using monoclonal antibody technology: results of a multicenter study in the United States. Cancer Res (Suppl) 46: 4237s-4240s, 1986
Thorpe SM: Monoclonal antibody technique for detection of estrogen receptors in human breast cancer: Greater sensitivity and more accurate classification of receptor status than the dextran coated charcoal method. Cancer Res 47: 6572–6575, 1987
Foekens JA, Portengen H, van Putten WLJ, Peters HA, Krijnen HLJM, Alexieva-Figusch, Klijn JGM: Prognostic value of estrogen and progesterone receptors measured by enzyme immunoassays in human breast tumor cytosols. Cancer Res 49: 5823–5828, 1989
Diem K, Lentner C: Scientific Tables, Ciba-Geigy Ltd, Basel, Switzerland, 7th edition, 1970, 145–197
Thorpe SM, Lykkesfelt AE, Vinterby A, Lonsdorfer M: Quantitative immunological detection of estrogen receptors in nuclear pellets from breast cancer biopsies. Cancer Res (Suppl) 46: 4251s-4255s, 1986
Leake RE, Benraad TJ: in preparation
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Blankenstein, M.A. Comparison of ligand binding assay and enzyme immunoassay of oestrogen receptor in human breast cancer cytosols. Breast Cancer Res Tr 17, 91–98 (1990). https://doi.org/10.1007/BF01806289
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DOI: https://doi.org/10.1007/BF01806289