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, Charles C. Guo, Nathalie Rioux-Leclercq, Andrea Haitel, Christian Bolenz, Karim Bensalah, Arthur I. Sagalowsky, Francesco Montorsi, Yair Lotan, Shahrokh F. Shariat, Brian D. RobinsonVitaly Margulis

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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.

Original languageEnglish
Pages (from-to)379-385
Number of pages7
JournalEuropean Urology
Volume66
Issue number2
DOIs
Publication statusPublished - 2014

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Keywords

  • Biomarker
  • Disease recurrence
  • Immunohistochemistry
  • IMP-3
  • Outcomes
  • Prognosis
  • Survival
  • Upper tract urothelial carcinoma

ASJC Scopus subject areas

  • Urology
  • Medicine(all)

Cite this

Lee, D. J., Xylinas, E., Rieken, M., Khani, F., Klatte, T., Wood, C. G., Karam, J. A., Weizer, A. Z., Raman, J. D., Remzi, M., Guo, C. C., Rioux-Leclercq, N., Haitel, A., Bolenz, C., Bensalah, K., Sagalowsky, A. I., Montorsi, F., Lotan, Y., Shariat, S. F., ... Margulis, V. (2014). Insulin-like growth factor messenger RNA-binding protein 3 expression helps prognostication in patients with upper tract urothelial carcinoma. European Urology, 66(2), 379-385. https://doi.org/10.1016/j.eururo.2013.12.008