Department of Pathology, University of Erlangen-Nuremberg, Erlangen, Germany.
Eur Urol. 2014 Jan;65(1):218-26. doi: 10.1016/j.eururo.2012.05.033. Epub 2012 May 19.
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.
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.
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.
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).
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.
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.
CK20、Ki-67 和 p53 的预后价值已在非肌肉浸润性膀胱癌中进行了研究，但在 pT1 膀胱癌这一独特且具有临床挑战性的亚组中尚未进行研究。
评估 CK20、Ki-67 和 p53 在最大系列 pT1 尿路上皮膀胱癌中的预后价值。
设计、地点和参与者：从一家泌尿科中心收集了 309 例 pT1 尿路上皮膀胱癌患者的数据。
每位患者均接受卡介苗膀胱内灌注。4-8 周后进行第二次切除。共有 76 例患者接受了膀胱切除术。
我们进行了组织形态学分析；对 CK20、Ki-67 和 p53 进行了免疫组织化学检测；并进行了单变量和多变量 Cox 回归模型分析，包括无复发生存率（RFS）、无进展生存率（PFS）和癌症特异性生存率（CSS）。
在中位随访 49 个月时，我们发现复发、进展和疾病特异性死亡率分别为 22.7%、20.1%和 15.9%。多变量分析显示 CK20 表达与 RFS 显著相关（风险比[HR]：5.89；95%置信区间[CI]，1.44-24.15；p=0.014）。多变量分析显示，Ki-67 是唯一与 PFS 显著相关的标志物（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）和 CK20（HR：8.44；95%CI，1.16-61.34；p=0.035）在多变量分析中与 CSS 显著相关。CK20 和 Ki-67 的组合在高增殖指数和异常 CK20 表达的肿瘤中显著影响 RFS（p=0.026）、PFS（p=0.003）和 CSS（p<0.001）。这是一项回顾性研究设计，是本研究的主要局限性。
我们目前对迄今为止发表的最大系列 pT1 尿路上皮膀胱癌患者的分析发现，Ki-67 和 CK20 可能是潜在的预后标志物，可改善 pT1 膀胱癌的风险分层。它们是生物侵袭性的可靠指标，可能有助于决策治疗策略 pT1 膀胱癌。
