Insulin-like Growth Factor Messenger RNA-binding Protein 3 Expression Helps Prognostication in Patients with Upper Tract Urothelial Carcinoma |
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| Authors: | 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 Charles C. Guo Nathalie Rioux-Leclercq Andrea Haitel Christian Bolenz Karim Bensalah Arthur I. Sagalowsky Francesco Montorsi Yair Lotan Shahrokh F. Shariat Brian D. Robinson Vitaly Margulis |
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| Affiliation: | 1. Department of Urology, Weill Cornell Medical College, New York, NY, USA;2. Inserm U955 Equipe 07, UPEC, Créteil, France;3. Department of Urology, Cochin Hospital, APHP, Paris Descartes University, Paris, France;4. Department of Urology, University Hospital Basel, Basel, Switzerland;5. Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA;6. Department of Urology, Medical University of Vienna, Vienna, Austria;g Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA;h Department of Urology, University of Michigan, Ann Arbor, MI, USA;i Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA;j Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA;k Department of Pathology, University of Rennes, Rennes, France;l Department of Pathology, Medical University of Vienna, Vienna, Austria;m Department of Urology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany;n Department of Urology, University of Rennes, Rennes, France;o Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA;p Department of Urology, Vita-Salute University, Milan, Italy |
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| Abstract: | BackgroundUpper 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.ObjectiveTo evaluate the association of the oncofetal protein IMP3 with oncologic outcomes in patients with UTUC treated with radical nephroureterectomy (RNU).Design, setting, and participantsWe 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.InterventionAll patients were diagnosed with UTUC and underwent RNU.Outcome measurement and statistical analysisUni- and multivariable Cox regression analyses evaluated the association of IMP3 protein expression with disease recurrence, cancer-specific mortality, and all-cause mortality.Results and limitationsIMP3 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.ConclusionsIMP3 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. |
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| Keywords: | IMP-3 Immunohistochemistry Upper tract urothelial carcinoma Biomarker Outcomes Prognosis Disease recurrence Survival |
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