Ki-67 Is an Independent Predictor of Bladder Cancer Outcome in Patients Treated with Radical Cystectomy for Organ-Confined Disease

Abstract

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. 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 with bladder TCC. We also assessed malignant lymph nodes from 50 of the 226 cystectomy patients. 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 analyses, 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) N(0); 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). 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.