QUANTITATION OF ESTROGEN CONCENTRATION IN CELLS

THE OBJECTIVE OF THIS PROJECT IS TO DEVELOP QUANTITATIVE ESTROGEN RECEPTOR CONCENTRATION MEASUREMENTS USING HIGH- RESOLUTION DIGITAL IMAGE MICROSCOPY TECHNIQUES. THE TECHNIQUES WILL ENABLE DIRECT MEASUREMENTS OF RECEPTOR CONCENTRATION ON A CELL-BY-CELL BASIS. THIS IS AN IMPROVEMENT OVER THE CURRENT BIOCHEMICAL ASSAYS, WHICH GIVE ONLY AN AVERAGE VALUE FOR RECEPTOR CONCENTRATION. THE QUANTITATIVE ASSAY PROPOSED FOR DEVELOPMENT WILL ALLOW FOR AMEASUREMENT OF THE HETEROGENEITY OF CONCENTRATION OF RECEPTORS IN CELL POPULATIONS AND THE PROPORTION OF CELLS INA TUMOR POPULATION THAT HAVE ESTROGEN RECEPTOR ABOVE A CERTAIN CONCENTRATION LEVEL. THE RECENT DEVELOPMENT OF MONOCLONAL ANTIBODIES AGAINST ESTROGEN RECEPTORS MAKES THE DEVELOPMENT OF METHODS FOR IMMUNOCYTOCHEMICAL LOCALIZATION OF ESTROGEN RECEPTORS FEASIBLE. ADDITIONAL RECENT ADVANCES IN QUANTITATIVE IMAGING CYTOLOGY CAN BE COMBINED WITH THIS TO DEVELOP A FAST, EFFICIENT, AND MORE ACCURATE ASSAY METHODAND TO ELIMINATE THE VISUAL SUBJECTIVE COMPONENTS OF THE METHOD. THIS COMBINATION OF THESE NEW TECHNIQUES TO PRODUCEA NEW QUANTITATIVE ASSAY IS PARTICULARILY IMPORTANT, AS IT HAS ALREADY BEEN SHOWN THAT PATIENTS WHOSE TUMORS CONTAIN ESTROGEN RECEPTORS WILL HAVE A HIGHER PROBABILITY OF RESPONDING TO HORMONAL THERAPY AND SEEM TO HAVE A BETTER PROGNOSIS THAN PATIENTS WHOSE TUMORS DO NOT CONTAIN THIS RECEPTOR.