Burger Maximilian, van der Aa Madelon N M, van Oers Johanna M M, Brinkmann Anke, van der Kwast Theodorus H, Steyerberg Ewout C, Stoehr Robert, Kirkels Wim J, Denzinger Stefan, Wild Peter J, Wieland Wolf F, Hofstaedter Ferdinand, Hartmann Arndt, Zwarthoff Ellen C
Department of Urology, University of Regensburg, Regensburg, Germany.
Eur Urol. 2008 Oct;54(4):835-43. doi: 10.1016/j.eururo.2007.12.026. Epub 2007 Dec 26.
The clinical management of non-muscle-invasive urothelial cell carcinoma of the bladder (UCC) is challenging, as it has a marked tendency to recur and to progress. Aim of this study was to investigate the prognostic value of the WHO 1973 and 2004 grading systems and biomarkers FGFR3, CK20 and Ki-67.
In a prospective study, tumours from 221 patients were studied for the expression of CK20 and Ki-67 by immunohistochemistry, and FGFR3 status by SNaPshot mutation detection. Staging and grading were performed according to the WHO classification systems of 1973 and 2004.
: Median follow-up was 35 mo. Recurrence occurred in 72 of 221 patients. None of the parameters was able to predict disease recurrence. CK20, Ki-67, FGFR3 mutation, molecular grade using FGFR3 mutation analysis and Ki-67, and histological grading and staging were significantly associated with disease progression in stage. In multivariable analyses, WHO 1973 and 2004 grading systems remained statistically significant and independent predictors of progression, with p=0.005 for WHO 1973 and p=0.004 for 2004. FGFR3 status was able to discriminate progressors from nonprogressors in a subset of patients with high-grade UCC (p=0.009).
This is the first prospective study comparing the WHO 1973 and 2004 grading systems. We show that both grading systems contribute valuable independent information. Therefore, it should be considered whether a better grading system could be developed that incorporates essential elements from both. The combination of WHO 2004 grading with FGFR3 status allows a better risk stratification for patients with high-grade non-muscle-invasive UCC.
膀胱非肌层浸润性尿路上皮癌（UCC）的临床管理具有挑战性，因为其具有明显的复发和进展倾向。本研究的目的是探讨世界卫生组织1973年和2004年分级系统以及生物标志物FGFR3、CK20和Ki-67的预后价值。
在一项前瞻性研究中，通过免疫组织化学研究了221例患者肿瘤中CK20和Ki-67的表达，并通过SNaPshot突变检测研究了FGFR3状态。根据世界卫生组织1973年和2004年分类系统进行分期和分级。
中位随访时间为35个月。221例患者中有72例复发。没有任何参数能够预测疾病复发。CK20、Ki-67、FGFR3突变、使用FGFR3突变分析的分子分级和Ki-67，以及组织学分级和分期与分期中的疾病进展显著相关。在多变量分析中，世界卫生组织1973年和2004年分级系统仍然是具有统计学意义的独立进展预测指标，1973年的p值为0.005，2004年的p值为0.004。FGFR3状态能够在一部分高级别UCC患者中区分进展者和非进展者（p=0.009）。
这是第一项比较世界卫生组织1973年和2004年分级系统的前瞻性研究。我们表明这两种分级系统都提供了有价值的独立信息。因此，应该考虑是否可以开发一种更好的分级系统，将两者的关键要素结合起来。世界卫生组织2004年分级与FGFR3状态的结合能够为高级别非肌层浸润性UCC患者提供更好的风险分层。
