Evaluation of a New Marker of the Ovarian Tumor Vasculature for Predicting Response to Treatment and as a Therapeutic Target

Abstract : The Follicle Stimulating Hormone receptor (FSHR) is a transmembrane cell surface receptor that binds FSH. The project is based on our observation that FSHR is highly expressed by the endothelial blood vessel cells in ovarian tumors. The experiments are aimed at characterizing FSHR expression levels in tumor sections using immunohistochemistry. The first goal is to determine if significant differences exist among the tumor types, and within the same tumor type, among tumor stages. The second goal is to evaluate the inhibitory effects on ovarian tumor angiogenesis and growth of an anti FSHR monoclonal antibody and of an antivascular agent. Using tumor tissue microarrays and a qualitative system of grading FSHR expression levels, we found that the main types of ovarian tumors and stages do not differ significantly in terms of vascular FSHR expression. A quantitative system was set-up for assessing FSHR expression, based on large tumor sections and quantitative determination of the density of FSHR-positive vessels at the interface between the tumor and the normal tissue. This more precise system offers better chances to detect differences among tumor types and stages. We found that FSHR-positive vessels are present in metastases of ovarian tumors to brain. We determined that the affinity of the anti FSHR monoclonal antibody 323 and / or its ability to suppress FSH/FSHR signaling is not sufficient to inhibit significantly tumor growth. Procedures to develop more efficient anti FSHR antibodies have been designed and are currently implemented. A cell line and a cell-ELISA type procedure, suitable for testing the agents targeted to FSHR in tumors, have been set-up.