Comparison of five histopathologic methods to assess cellular proliferation in transitional cell carcinoma of the urinary bladder.

Transitional cell carcinomas of the urinary bladder vary in their biologic potential, which may be correlated with the grade and stage of the tumor. Cellular proliferation may prove to be another measure of predicting tumor biologic potential. We have compared five different methods to assess proliferation in 26 tumors and correlated these results with tumor grade and stage. A portion of each tumor was incubated in vitro with bromodeoxyuridine (BrdUrd). For each tumor this was compared with at least three of the following four other markers of proliferation: mitotic count, silver-stained nucleolar organizer regions, immunohistochemical staining with Ki67, and proliferating cell nuclear antigen. Statistical correlations were seen between tumor grade and stage and these markers. There were strong correlations between the BrdUrd labeling index (LI) and both the Ki67 LI and proliferating cell nuclear antigen LI. The correlation between the BrdUrd LI and mitotic count was more tenuous; no significant correlation was found between BrdUrd LI and silver-stained nucleolar organizer region count. The correlation between these measurements of proliferation and tumor grade and stage was less strong. Our data suggest that cellular proliferation of transitional cell carcinomas can be reliably assessed with several different markers and that most of these markers can be correlated with tumor grade but not with stage.