Immunohistochemical method for the detection of defective estrogen receptors

摘要

Identification of defective ER and subclassifying ER+ breast cancers on the basis of the presence of defective ER is described as a tool potentially useful, as previously shown by the results of a pilot study, for predicting which among the ER+ tumors will respond and which will fail to repsond to hormonal modes of therapy. Improvements are introduced in the specimen sampling and ligand introduction steps of the immunohistochemical procedure which was developed for sub-classifying estrogen receptor-positive tumors of human breast cancers and other cancers of the estrogen target organs on the basis of the presence of defective estrogen receptors. Additionally, a new monoclonal antibody reagent which has potential use as a replacement for the polyclonal anti- ER antibody reagents is also described. The modified steps include the use of tumor imprints instead of cryosections; use of ligand coated slides instead of the original ligand layering step. Both these modifications which simplified the execution of the test procedure and the availability of a suitable monoclonal antibody reagent should facilitate wider use and automation of the entire procedure if needed. Methodology for the application of this modified test procedure for rapidly screening drug compounds to detect which affect the translocation behaviour of defective ER and as a simple tool for identifying the presence of components in water and other solutions which might be toxic to the normal non-defective estrogen receptors found in normal tissues are also presented.