Combination of CK20 and Ki-67 immunostaining analysis predicts recurrence, progression, and cancer-specific survival in pT1 urothelial bladder cancer

Abstract

Background: The prognostic value of CK20, Ki-67, and p53 has been investigated for non-muscle-invasive urothelial bladder cancers but not for the distinct and clinically challenging subset of pT1 bladder cancers.

Objective: To evaluate the prognostic value of CK20, Ki-67, and p53 within the largest series of pT1 urothelial bladder cancers.

Design, setting, and participants: Data from 309 patients with pT1 urothelial bladder cancer from one single urologic centre were collected.

Intervention: Adjuvant instillation of bacillus Calmette-Guérin was performed in each patient. A second resection was performed after 4-8 wk. A total of 76 patients underwent cystectomy.

Outcome measurements and statistical analysis: We conducted histomorphologic analysis; immunohistochemistry for CK20, Ki-67, and p53; and univariate and multivariate Cox regression models including recurrence-free survival (RFS), progression-free survival (PFS), and cancer-specific survival (CSS).

Results and limitations: At a median follow-up of 49 mo, we found recurrence and progression and disease-specific mortality rates of 22.7%, 20.1%, and 15.9%, respectively. CK20 expression was significantly correlated with RFS in multivariate analysis (hazard ratio [HR]: 5.89; 95% confidence interval [CI], 1.44-24.15; p=0.014). In multivariate analysis, Ki-67 was the only marker significantly correlated with PFS (HR: 2.80; 95% CI, 1.45-5.43, p=0.002). Ki-67 (HR: 3.83; 95% CI, 1.59-9.26; p=0.003), and CK20 (HR: 8.44; 95% CI,1.16-61.34; p=0.035) were significantly correlated with CSS in multivariate analysis. The combination of CK20 and Ki-67 showed significantly worse RFS (p=0.026), PFS (p=0.003), and CSS (p<0.001) in tumours with a high proliferation index and abnormal CK20 expression. A retrospective study design was the major limitation of this study.

Conclusions: Our present analysis of the largest series of patients with pT1 urothelial bladder cancer published to date found Ki-67 and CK20 to be potential prognostic markers improving the risk stratification of pT1 bladder tumours. They are reliable indicators of biologic aggressiveness and may contribute to decision making on therapeutic strategy for pT1 bladder carcinomas.

Keywords: Disease progression; Immunohistochemistry; Recurrence; Risk assessment; Urinary bladder carcinoma; pT1 bladder cancer.