Influence of estrogen receptor variants in mammary carcinomas on the prognostic reliability of the receptor assay.

We have used GR mouse mammary carcinomas as a model for evaluating the effect of estrogen receptor (ER) variants, present in the tumor cytosols, on the prognostic reliability of the receptor assay. Rapid, high resolution procedures were used for the assessment of wild-type and variant estrogen receptors in the cytosols of hormone-responsive and nonresponsive mammary tumors of GR mice. Two main ER types were resolved by high performance ion-exchange and size-exclusion chromatography: the wild-type receptor (II), and a fraction representing low molecular weight ER (I). ER types I and II both bound estradiol and both reacted with the anti-ER monoclonal antibodies H222 and D547 whose epitopes are in the C-terminal part of ER. The level of ER type II was higher in hormone-responsive than in hormone-nonresponsive tumors, whereas ER type I was about equally low in both types of tumor groups. ER types I and II both influence the standard ligand binding and antibody binding (Abbott EIA) test, but only the wild-type ER causes hormone-responsive growth of the tumor. These data suggest that prognostic clinical tests, currently in use for estimating ER in tumors of breast cancer patients, may be impaired by the presence of low molecular weight estrogen receptor variants in the tumor samples.