S phase fraction of human bladder tumor measured in situ with bromodeoxyuridine labeling

A total of 18 patients with transitional cell bladder cancer was given a 0.5-hour intravenous infusion of bromodeoxyuridine at the time of endoscopic biopsy or transurethral resection to label tumor cells in the deoxyribonucleic acid synthesis phase (S phase). The tumor specimens were fixed with 70 per cent ethanol, embedded in paraffin, sectioned and stained by an indirect immunoperoxidase method with anti-bromodeoxyuridine monoclonal antibody as the first antibody. The bromodeoxyuridine labeling index, S phase fraction, was determined by counting the number of bromodeoxyuridine-labeled cells in the tissue sections. All grade 1 tumors had an S phase fraction of lower than 10 per cent. The average S phase fractions for noninvasive (11 cases) and invasive (7) tumors were 9.8 and 20.0 per cent, respectively. Two distant metastatic bladder tumors showed an average S phase fraction of 25.3 and 30.0 per cent. Thus, transitional cell bladder cancers with an S phase fraction of greater than 10 per cent appears to grow faster and be more invasive more often than those with an S phase fraction of less than 10 per cent. The higher S phase fraction may indicate greater biological malignancy. Our preliminary results suggest that measurement of the bromodeoxyuridine labeling index in bladder tumors may be a new objective and quantitative assay of biological potential of individual tumors.