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Insulin-like Growth Factor Messenger RNA-binding Protein 3 Expression Helps Prognostication in Patients with Upper Tract Urothelial Carcinoma

Daniel J. Lee; Evanguelos Xylinas; Malte Rieken; Francesca Khani; Tobias Klatte; Christopher G. Wood; Jose A. Karam; Alon Z. Weizer; Jay D. Raman; Mesut Remzi; et al.

(Profiled Authors: Yair Lotan; Vitaly Margulis; Arthur I Sagalowsky)

European Urology. 2014.

Abstract

Background: Upper tract urothelial carcinoma (UTUC) is a clinically heterogeneous disease that lacks high-quality trials that provide definitive prognostic markers. Insulin-like growth factor messenger RNA binding protein 3 (IMP3) has been associated with outcomes in urothelial carcinoma of the bladder but was not yet studied in UTUC. Objective: To evaluate the association of the oncofetal protein IMP3 with oncologic outcomes in patients with UTUC treated with radical nephroureterectomy (RNU). Design, setting, and participants: We investigated the expression of IMP3 and its association with clinical outcomes using tissue microarrays constructed from 622 patients treated with RNU at seven international institutions between 1991 and 2008. Intervention: All patients were diagnosed with UTUC and underwent RNU. Outcome measurement and statistical analysis: Uni- and multivariable Cox regression analyses evaluated the association of IMP3 protein expression with disease recurrence, cancer-specific mortality, and all-cause mortality. Results and limitations: IMP3 was expressed in 12.2% of patients with UTUC (n = 76). The expression was tumor specific and correlated with higher stages/grades. Within a median follow-up of 27 mo (interquartile range [IQR]: 12-53), 191 patients (25.4%) experienced disease recurrence, and 165 (21.9%) died of the disease. Patients with IMP3 demonstrated significantly worse recurrence-free survival (27.4% vs 75.1%; p < 0.01), cancer-specific survival (34.5% vs 78.9%; p < 0.01), and overall survival (15.6% vs 64.8%; p < 0.01) at 5 yr compared with those without IMP3. In multivariable Cox regression analyses, which adjusted for the effects of standard clinicopathologic features, IMP3expression was independently associated with disease recurrence (hazard ratio [HR]: 1.87; p < 0.01), cancer-specific mortality (HR: 2.15; p < 0.01), and all-cause mortality (HR: 2.07; p < 0.01). Major limitations include the retrospective design and relatively short follow-up time. Conclusions: IMP3 expression is independently associated with disease recurrence, cancer-specific mortality, and all-cause mortality in UTUC. IMP3 may help improve risk stratification and prognostication of UTUC patients treated with RNU. © 2013 European Association of Urology.

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