Prognostic value of the proliferative index determined by Ki-67 immunostaining in superficial bladder tumors

The biological behavior of urothelial carcinomas remains unpredictable. The objective of this study was to determine the prognostic value of Ki-67 ind ex in superficial papillary bladder tumors and to correlate it with the S-p hase fraction (SPF] measured by flow cytometry. Three hundred nineteen pati ents with newly diagnosed superficial (pTa, pT1) bladder tumors were includ ed between September 1990 and April 1992. Patients with bladder carcinoma i n situ alone were excluded. We observed 255 pTa tumors and 64 pT1 tumors, w hereas 111 lesions were classified as grade G1 and 208 as grade G2-G3. Ki-6 7 immunostaining was performed on paraffin-embedded material using a 3-step immunoperoxidase procedure with the murine monoclonal antibody MiB1. The r elation between Ki-67 expression and prognostic variables (stage, grade, tu mor size, multifocality age, and sex) was investigated by the chi-square te st. Cox regression was used to describe the association between Ki-67 and t umor recurrence in 308 patients with follow-up while adjusting for potentia lly confounding prognostic variables. The frequency of high Ki-67 expressio n (greater than or equal to 10%) increased with stage (P = .005) and grade (P = .001), but not with tumor size or multifocality. Two hundred one patie nts experienced tumor recurrence in a median follow-up of 65 months. Stage, grade, tumor size, and multifocality were all independent predictors of re currence. Ki-67 index greater than 10% tvas found to be an independent pred ictor of tumor recurrence among patients with tumors larger than 3 cm in di ameter (HR = 2.05, CI = 1.18-3.55), but not those with smaller size tumors. With regards to the DNA index, a significant but weak correlation tvas obs erved between Ki-67 expression and the SPF (Spearman's correlation coeffici ent = 0.23, P = .004). In addition, aneuploid tumors had significantly high er expression of Ki-67 (22.5%) than diploid tumors (10.1%) (P = .0006). Mor eover, patients with DNA aneuploid bladder tumors were more likely to have mere than 10% Ki-67-positive cells than those with diploid tumors. In patie nts with newly diagnosed pTa or pT1 bladder tumors, a Ki-67 index above 10% is an independent predictor of shorter time to recurrence only in those wi th tumors larger than 3 cm. Copyright (C) 1999 by W.B. Saunders Company.