Clinical implications of urokinase and tissue type plasminogen activators and their inhibitor (PAI-1) in breast cancer tissue.

Cytosol of primary breast cancers from 217 women of predominantly Arab ethnicity were assayed for uPA, tPA, PAI-1 and a subset for ER, PR and pS2. Serum levels of CEA and CA153 were determined during follow-up. Only tPA correlated to nodal status and tumour grade, and PAI-1 to clinical stage. PAI-1 was related to uPA and both were inversely correlated with PR and pS2 (PAI-1 also to ER). Conversely tPA was directly correlated with ER, PR and pS2. Women with high tumour uPA and PAI-1, but not tPA, had shorter overall, and relapse-free, survival. Only nodal status and clinical stage were independent predictors in multivariate analysis. However, uPA and PAI-1 were more prognostically informative than ER or PR and their usefulness may extend to delineation of patients likely to respond to adjuvant therapy.

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 tissue from a total of 799 patients, measuring both oestrogen and progesterone receptors (ER, PR) using either the ligand binding assay (LBA) or the enzyme immunoassay technique (EIA). Mean and median receptor levels 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 for clinical evaluation, was also lower than that reported by the EORTC Receptor Study Group. Although the measurements comparing the 2 methods were statistically correlated in terms of positivity, based on the above criteria for clinical assessment, concordance was considered to be relatively poor, particularly for ER when assayed in the same samples by the 2 methods. In cytosolic but not nuclear extracts, the LBA method gave a higher median value for ER than the EIA (except in the group 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 excellent correlation between receptor amounts in cytosolic and nuclear extracts for both ER and PR using the EIA; this was significantly better than with LBA. We also observed a correlation between ER and PR in both 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 only when the EIA method was used. We conclude that the EIA method appears to be more sensitive and gives biologically more reliable results. However, the disagreement between the methods may be due to legitimate recognition of altered forms of the receptor and may be of biological significance. Although the presence of receptor in the cytosolic fraction is artifactual, its measurement by EIA does parallel the amounts of nuclear receptor, which may be a more relevant biological parameter.