Inter-site variation of oestrogen receptors in human breast cancers

Abstract

When large human breast cancers were assayed for oestrogen receptors at multiple sites, 5-fold differences were found in the numbers of oestrogen receptors, between the site within a tumour. This may result from variations in the cell:stroma ratio from site to site. Such differences could be significant when receptor levels in the tumour are low (less than 50 fmol oestradiol bound mg cytosol protein) since the classification distinction between hormone-sensitive and hormone-insensitive breast cancers is based upon numbers of oestrogen receptors detected by the assay. This problem might be remedied by assessment of the cell:stroma ratio in all assayed tumours, and by the combination of the cytoplasmic oestrogen-receptor assay with other hormone-receptor assays.

PIP: Both human mammary gland tumors and human myometrium were used to examine the inherent variability of the estrogen-receptor assay of cytosol fractions derived from the tumors and to report results of assays on multiple sites within large breast cancers. Cytosol and tissue assays of human myometrium showed only small variability in binding site numbers between assays of the same fractions. However, estrogen-receptor assays performed on multiple sites in large receptor-positive mammary gland tumors showed marked intersite variation within each tumor, with up to a 4-fold difference (e.g., a range of 175-523 sites in 1 tumor). This difference may result from variation in the cell:stroma ratio from site to site. In the majority of tumors (5), this variability did not affect classification of receptor status, but in 2 tumors, this variation was significant where receptor levels in the tumors were low ( 50 fmol estradiol bound). Resolution of this assay problem may be achieved by combining: 1) assessment of cell:stroma ratio of the assayed site; 2) estimation of nuclear receptors for estrogen; and 3) estimation of progesterone receptors.