STEROID-RECEPTOR MEASUREMENT IN BREAST CANCERS - COMPARISON BETWEEN LIGAND-BINDING AND ENZYME-IMMUNOASSAY IN CYTOSOLIC AND NUCLEAR EXTRACTS

We have analysed cytoplasmic and nuclear extracts of breast-cancer tis sue from a total of 799 patients, measuring both oestrogen and progest erone receptors (ER, PR) using either the ligand binding assay (LBA) o r the enzyme immunoassay technique (EIA), Mean and median receptor lev els were much lower than those widely reported by others, For ER, this may in part be a consequence of the younger median age of the patient group, The frequency of positivity, using consensus cut-off values fo r clinical evaluation, was also lower than that reported by the EORTC Receptor Study Group, Although the measurements comparing the 2 method s were statistically correlated in terms of positivity, based on the a bove criteria for clinical assessment, concordance was considered to b e relatively poor, particularly for ER when assayed in the same sample s by the 2 methods. In cytosolic but not nuclear extracts, the LBA met hod gave a higher median value for ER than the EIA (except in the grou p that had EIA values greater than 15 fmol/mg protein); for PR, median values were higher with EIA in both cell fractions., There was an exc ellent correlation between receptor amounts in cytosolic and nuclear e xtracts for both ER and PR using the EIA; this was significantly bette r than with LBA, We also observed a correlation between ER and PR in b oth cytosolic and nuclear fractions which was most pronounced when the analysis was done by EIA, The amounts of ER in the cytosolic fraction were also correlated with the those of PR in the nuclear fraction and ER in the nuclear fraction with PR in the cytosolic fraction, but onl y when the EIA method was used. We conclude that the EIA method appear s to be more sensitive and gives biologically move reliable results, H owever, the disagreement between the methods may he due to legitimate recognition of altered forms of the receptor and may be of biological significance, Although the presence of receptor in the cytosolic fract ion is artifactual, its measurement by EIA does parallel the amounts o f nuclear receptor, which may be a more relevant biological parameter, (C) 1997 Wiley-Liss, Inc.