Cellular markers for prognosis in human bladder cancer will be identified and validated. The goal is to predict accurately the probability of recurrence or progression for individual tumors, thereby contributing to patient management and understanding of the pathobiology of bladder tumors. Nuclear DNA content, cytokinetics, chromatin distribution patterns, oncogene expression, and in situ cytogenetics will be quantified by image and flow cytometry. Additional markers, developed by colleagues, the marker network, or elsewhere will be evaluated when appropriate. Retrospective studies will access tissue blocks from 200 cases with known outcomes. DNA content, chromatin pattern, and oncogene expression will be quantified. The diagnostic and predictive power of these measurements will be established. Prospective studies will access 100 new patients per year. Specimens include initial surgical biopsies, urines, and bladder irrigations, and four-monthly follow-up urines and irrigations. Adequately cellular specimens will be incubated with 5-BrdUrd for cytokinetic studies. Analysis includes: cellular DNA content, proliferation index, chromatin pattern, oncogene expression, in situ cytogenetics by hybridocytochemistry, and immunocytochemical markers. Cells in urine and irrigation specimens will be pelleted and embedded: sections from these samples and from the tissue blocks will be available for subsequent analysis and for distribution to other network laboratories. In all cases, marker results will be evaluated against histologic and cytologic findings and against patient outcome in order to identify markers that accurately predict tumor recurrence, progression, and therapeutic response, and patient morbidity and mortality.
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