EVALUATION OF DNA FLOW-CYTOMETRY AS A SCREENING-TEST FOR BLADDER-CANCER

At this present time, we feel that there is no role for DNA flow cytometry (FCM), or indeed DNA studies by any other method, to be used as a screening procedure for patients with no prior history of bladder cancer due to the high false-positive rate found when monitoring exfoliated urothelial cells. On the other hand, for patients who have had a superficial transitional cell carcinoma (TCC), which has a documented 50% recurrence rate, and depending on pathological features, a progression rate from 7 to 45%, DNA FCM provides a sensitive method to predict future disease recurrence. It provides an extremely effective way to predict future progression and further acts as a method to monitor changes in the malignant potential of the patient's disease. For those patients with a past history of superficial TCC who develop abnormal ploidy without any overt tumor, 80% will, within the next four years, suffer a disease recurrence. For the patient who has a Ta TCC and receives intravesical Bacillus Calmette-Guerin (BCG), the development of abnormal ploidy in bladder washing specimens is the single best indicator for future disease recurrence. Similarly, a negative DNA FCM of a bladder washing at six months after intravesical therapy is an excellent predictor of no further occurrence. In patients with superficial TCC, ploidy of the initial and recurrent tumor predicts for future progression. Half of those patients with stage Ta bladder cancer with two successive aneuploid bladder tumors develop muscle invasive disease within one year, while three-fourths develop advanced disease within two years after recurrence of their second aneuploid lesion. There is a group of patients for whom false-negative results may present a serious problem. These are patients with microhematuria of unknown etiology. We will illustrate how a protein counterstain and two-parameter DNA-protein histograms may be used to eliminate the signals from the extraneous leukocytes and permit detection of relatively small numbers of aneuploid cells by FCM. It is highly probable that bladder cancer, like other types of cancer, develops as a result of a series of somatic mutations. Two-parameter DNA fluorescent antibody study of normal, mutant and deleted oncogenes or tumor suppressor genes offers tremendous promise in monitoring the clinical course of bladder cancer. As a paradigm for the study of bladder cancer, we will illustrate FCM detection of the p53 protein product in archival prostate tissue. Monoclonal antibody studies offer exciting prospects for the better detection and characterization of TCC. Screening for this disease may, in the future, employ a dipstick method. For people with a past history of bladder cancer or who are found to have current disease, the number of markers which can be measured by either FCM or image analysis will be the key to determining the malignant potential and the sensitivity of the tumor to therapy.