BLADDER-CANCER RISK ASSESSMENT WITH QUANTITATIVE FLUORESCENCE IMAGE-ANALYSIS OF TUMOR-MARKERS IN EXFOLIATED BLADDER CELLS

Background. The detection of potentially highly curable low-grade blad der cancers by noninvasive techniques remains an unsolved problem. Con ventional cytology detects such tumors with 50% sensitivity, and addit ion of DNA measurements to cytology only improves sensitivity incremen tally. Tumor-associated antigens potentially offer an additional diagn ostic marker. Methods. In this study, the M344 antibody against a tumo r-associated antigen expressed mainly by low-grade tumor cells was tes ted for its sensitivity and specificity, alone and in combination with DNA ploidy and cytology. Voided urine samples from 69 asymptomatic co ntrol subjects, urines and bladder washings from 59 patients with canc er, and 195 symptomatic control patients were collected. Cells were do uble-labeled with M344 monoclonal antibody and Hoechst. Each case was blinded, and the number of positive cells was scored by two independen t observers. Results. High-grade and low-grade transitional cell carci nomas (TCC) were detected with equal efficiency (78%, P < 0.001 versus symptomatic control patients). Urine samples proved higher specificit y in detecting cancers. Patients being monitored for recurrence, but w ithout current detectable cancer, were intermediates between control s ubjects and patients with cancer, suggesting that this marker also res ponds to dysplasia or field disease. Patients with outlet obstruction did not significantly differ from patients with previous TCC (P = 0.95 ). When combined with DNA ploidy measurements and cytology, the sensit ivity for low-grade and high-grade tumors was 88% and 95%, respectivel y. Conclusions. The M344 antibody potentially could improve the specif icity and sensitivity of detection of low-grade bladder tumors in symp tomatic and asymptomatic patients as well as monitoring for recurrence , therapeutic response, and assessment of individual risk.