FLUORESCENT STEROID BINDING IN ENDOMETRIAL CARCINOMA

TUMOR SAMPLES FROM WOMEN WITH ENDOMETRIAL CARCINOMA ARE RARELY ASSAYED FOR STEROID BINDING SITES ALTHOUGH IT IS COMMON KNOWLEDGE THAT THEY ARE OFTEN PROGESTIN-SENSITIVE. HORMONAL THERAPY, IF GIVEN, IS NEARLY ALWAYS ADMINISTERED ON AN EMPIRICAL BASIS. CONVENTIONAL BIOCHEMICAL ESTROGEN (ER) AND PROGESTERONE RECEPTOR (PGR) ASSAYS ARE VERY DIFFICULT TO PERFORM IN THIS MALIGNANCY SINCE SPECIMENS OFTEN CONTAIN ADMIXTURES OF BENIGN, HYPERPLASTIC AND MALIGNANT GLANDULAR ELEMENTS, STROMA AND MYOMETRIUM, ALL OF WHICH MAY CONTRIBUTE RECEPTOR TO A TUMOR CYTOSOL. THIS PROJECT PLANS TO STUDY INTACT TISSUE SECTIONS OF ENDOMETRIAL TUMOR TISSUE FOR ESTROGEN AND PROGESTERONE BINDING SITES USING FLUORESCEIN TAGGED STEROID CONJUGATES OFESTROGEN AND PROGESTERONE (FLUORO-CEP(R)) WHICH ALLOW FOR LOCALIZATION OF STEROID BINDING SITES AT A CELLULAR AND SUBCELLULAR LEVEL. EVENTUALLY, ASSAY RESULTS WILL BE CORRELATED WITH A VARIETY OF CLINICAL AND PATHOLOGICAL FEATURES INCLUDING AGE, MENOPAUSAL STATUS, TUMOR GRADE AND STAGE. IN THE PRESENT STUDY, RESULTS WILL ALSO BE CORRELATED WITH THOSE OF IMMUNOCYTOCHEMICAL ASSAYS EMPLOYINGMONOCLONAL ANTIBODIES TO ESTROGEN AND PROGESTERONE AND, WHERE SUFFICIENT TISSUE IS AVAILABLE, WITH RESULTS OF CONVENTIONAL BIOCHEMICAL ER AND PGR ASSAYS. THE ULTIMATE GOAL OF THESE STUDIES IS TO DEVELOP AN INEXPENSIVE METHOD TO ACCURATELY ASSAY FOR ENDOMETRIAL TUMOR STEROID BINDING SITES WHICH WILL HELP CLINICIANS IN THE SELECTION OFA MORE RATIONAL THERAPY FOR PATIENTS WITH ADVANCED CARCINOMA. THE ASSAY SHOULD BE CAPABLE OF PERFORMANCE IN THE AVERAGE COMMUNITY HOSPITAL PATHOLOGY LABORATORY. PHASE I OF THESE STUDIES WILL CONCERN ITSELF WITH A PRELIMINARY COMPARISON OF FLUORO-CEP(R) WITH OTHER HISTOCHEMICAL AND BIOCHEMICAL PROCEDURES FOR DETECTION OF ER AND PGR.