Ki-67 is an independent predictor of bladder cancer outcome in patients treated with radical cystectomy for organ-confined disease

Purpose: To determine the association of the cell proliferative marker Ki-67 with pathologic features and disease prognosis in patients with transitional cell carcinoma (TCC) of the urinary bladder. Methods: Immunohistochemical staining for Ki-67 was done on serial cuts from tissue microarrays containing cystectomy specimens from 9 patients without bladder cancer and 226 consecutive patients wit bladder TCC. We also assessed malignant lymph nodes from 50 of the 226 cystectomy patients. Results: Ki-67 expression was increased in 42.5% cystectomy specimens and in 54% metastatic lymph nodes. In contrast, it was absent in all nine benign cystectomy specimens. Ki-67 overexpression was associated with advanced pathologic stage, higher grade, lymphovascular invasion and metastases to lymph nodes (P = 0.001, 0.040, 0.031 and 0.036, respectively). In multivariate analysis, pathologic stage and lymph node metastases were independent predictors of disease recurrence and bladder cancer specific mortality. In the subgroup of patients with organ-confined disease (<pT(3) No; n = 91), excluding patients who received neoadjuvant or adjuvant chemotherapy, Ki-67 status was an independent predictor of both disease recurrence (risk ratio 7.591, P = 0.001) and bladder cancer specific mortality (risk ratio, 4.045 P = 0.041). Conclusions: Ki-67 overexpression is associated with features of aggressive bladder TCC and adds independent prognostic information to standard pathologic features for prediction of clinical outcome after radical cystectomy.