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 bladder cancers by noninvasive techniques remains an unsolved problem. Conventional cytology detects such tumors with 50% sensitivity, and addition of DNA measurements to cytology only improves sensitivity incrementally. Tumor-associated antigens potentially offer an additional diagnostic marker.


METHODS
In this study, the M344 antibody against a tumor-associated antigen expressed mainly by low-grade tumor cells was tested for its sensitivity and specificity, alone and in combination with DNA ploidy and cytology. Voided urine samples from 69 asymptomatic control subjects, urines and bladder washings from 59 patients with cancer, and 195 symptomatic control patients were collected. Cells were double-labeled with M344 monoclonal antibody and Hoechst. Each case was blinded, and the number of positive cells was scored by two independent observers.


RESULTS
High-grade and low-grade transitional cell carcinomas (TCC) were detected with equal efficiency (78%, P < 0.001 versus symptomatic control patients). Urine samples proved higher specificity in detecting cancers. Patients being monitored for recurrence, but without current detectable cancer, were intermediates between control subjects and patients with cancer, suggesting that this marker also responds 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 sensitivity for low-grade and high-grade tumors was 88% and 95%, respectively.


CONCLUSIONS
The M344 antibody potentially could improve the specificity and sensitivity of detection of low-grade bladder tumors in symptomatic and asymptomatic patients as well as monitoring for recurrence, therapeutic response, and assessment of individual risk.
Bonner
R B
RB
Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Hemstreet
G P
GP
Fradet
Y
Y
Rao
J Y
JY
Min
K W
KW
Hurst
R E
RE
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis; D002295:Carcinoma, Transitional Cell / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology / Q000652:urine; D004273:DNA, Neoplasm / Q000032:analysis; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D009077:Mucins / Q000032:analysis; D011003:Ploidies; D011237:Predictive Value of Tests; D012307:Risk Factors; D012680:Sensitivity and Specificity; D001743:Urinary Bladder / Q000737:chemistry / Q000276:immunology / Q000473:pathology*; D001749:Urinary Bladder Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000276:immunology / Q000652:urine; D014556:Urine / Q000166:cytology
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D006023:Glycoproteins; D009077:Mucins