SBIR-STTR Award

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 of estrogen and progesterone (Fluore-Cep) which allows 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 o immunocytochemical assays employing monoclonal 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 istes which will help clinicians in the selection of a 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 with other histochemica and biochemical procedures for detection of ER and PgR.National Cancer Institute (NCI)

Tumor tissue from women with endometrial carcinoma is almost never assayed for steroid hormone receptors although many of these cancers are progestin sensitive. Hormonal therapy, if given, is nearly always administered on an empirical basis. Conventional biochemical estrogen (ER) and progesterone receptor (PgR) assays are difficult to perform and interpret in this malignancy because specimens often contain admixtures of benign, hyperplastic, and neoplastic epithelium, stroma, and myometrium, all of which may contribute receptor to a tumor cytosol.This study will examine steroid hormonebinding sites in tissue sections of endometrial carcinoma using fluorescein and rhodamine-tagged conjugates of estrogen and progesterone that allow for localization of receptor at a cellular and subcellular level. Assay results will be correlated with those of immunocytochemistry using specific monoclonal, antireceptor antibodies and, where possible, with biochemical ER and PgR assay values. All results will be correlated with a variety of clinical and pathological features, in particular with clinical endocrine response, disease-free interval, and survival. The ultimate goal is to identify the best possible assay that could be performed in a community hospital laboratory that would aid clinicians in the selection of the most rational therapies for endometrial carcinoma.Awardee's statement of the potential commercial applications of the research:The availability of an inexpensive method for the in situ detection of steroid-binding sites in endometrial carcinoma capable of performance at the community hospitai level, will enable selection of a more rational therapy for many women with advanced disease than is currently possible. Such a test would have worldwide commercial applications.National Cancer Institute (NCI)