5-Bromodeoxyuridine incorporation and PCNA expression as measures of cell proliferation in transitional cell...

Cell proliferation in 66 transitional cell carcinomas of the human urinary bladder was evaluated using immunohistochemical detection of in vitro 5-bromodeoxyuridine (BrdUrd) incorporation and of proliferating cell nuclear antigen (PCNA). The labeling index (LI) was defined as percent of labeled nuclei for 2000 tumor nuclei counted. The BrdUrd LI ranged from 0.2% to 38.9%, geometric mean = 8.4% (n = 61), and the PCNA LI ranged from 0.4% to 64.1%, geometric mean = 12.7% (n = 60). For the 55 tumors that were stained by both procedures, the BrdUrd LI showed a highly significant regression on the PCNA LI (BrdUrd LI = 0.74 * PCNA LI, R2 = 0.71, p < 0.0001, coefficient of variation of residual = 17.7%, log transformed data). When compared to clinical and histopathologic criteria, both labeling indices were substantially lower in low grade (Grade 1) versus high grade (Grades 2 and 3) tumors and in Ta tumors versus higher stage T1, T2, and T3 tumors. These studies show that BrdUrd incorporation can be used reliably to measure cell proliferation in fresh bladder tissue, that PCNA labeling is a similar measure of cell proliferation, and that both measures are low in tumors of low histopathologic grade and stage.