Cell proliferation of human bladder tumors determined by BrdUrd and Ki-67 immunostaining

The cell proliferation of bladder tumors was assessed in situ using BrdUrd (bromodeoxyuridine) and Ki-67 immunostaining. BrdUrd is incorporated into S-phase cells, and Ki-67 monoclonal antibody recognizes a nuclear antigen present in proliferating, but not resting cells. The percentage of labeled cells was expressed as the labeling index (LI). The average BrdUrd LI obtained applying this method to normal epithelium and to transitional cell carcinoma were 4.1% and 13.1%, respectively, while the Ki-67 LI had average values of 6.2% and 17.8%, respectively. Labeled cells were distributed throughout both the basal and surface layers of transitional cell carcinoma. In general, the value of the BrdUrd LI was correlated to that of the Ki-67 LI. A relatively large fraction of labeled cells was found in high grade or invasive tumors. Bladder tumors with lymph node involvement had higher LI than those without. In addition, a high frequency of S-phase cells within tumor tissue appeared to indicate a great potential for malignancy and thus a poor prognosis. These findings indicate that immunostaining with BrdUrd and Ki-67 may be useful tools for easy and quick evaluation of proliferating cells in bladder tumors.