MARKERS OF EXFOLIATED BENIGN AND MALIGNANT BLADDER CELLS

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Our overall objective is the evaluation of existing and newly developed monoclonal antibodies as potential tumor markers of exfoliated bladder epithelial cells, and to identify those markers of potential clinical value in detection of bladder tumors, predicting their behavior and response to therapy. The specific aims fall within three categories: 1) to rigorously test the sensitivity and specificity of binding to bladder tumor cells by a panel of 32 well characterized and presently available monoclonal antibodies to cell surface tumor-associated antigens, blood group related antigens, cytostructural antigens, oncogene- coded products, and growth factor receptors, (a) by immunohistochemistry on tissue sections of human bladder tumors, reactive or metaplastic urothelium in inflammatory processes and normal urothelium, (b) by immunocytochemistry on cytology smears of exfoliated bladder epithelial cells from patients with bladder tumors, cystitis and normal mucosa, (c) flow cytometry of bladder irrigation specimens and cell suspensions from resected tumors using dual parameter DNA/monoclonal antibody binding measurements and three parameter-dual laser DNA/double monoclonal antibody binding, 2) to correlate the antigenic phenotype of bladder tumors analyzed with (a) conventional histopathologic and cytologic features and flow cytometry parameters, (b) clinical course including tumor progression, metastases, and response to therapy, and 3) to establish a new subclassification of human bladder tumors based on immunophenotypic features reliable and useful in clinical management and prognosis. Our evaluation will involve comparative analysis of the cytology of exfoliated bladder epithelial cells, histology of resected tumors, flow cytometry of cell suspensions and bladder irrigation specimens, cystoscopy and biopsy findings; and a sequential evaluation of all the parameters mentioned above during follow- up of patients treated conservatively. These multiparameter analyses of human bladder tumors are expected to yield new markers for immunodiagnosis and important information about cellular differentiation and transformation.