title: Insulin-like growth factor messenger RNA-binding protein 3 expression helps prognostication in patients with upper tract urothelial carcinoma.
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).
  
  
  METHODS
  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.
  
  
  METHODS
  All patients were diagnosed with UTUC and underwent RNU.
  
  
  METHODS
  Uni- and multivariable Cox regression analyses evaluated the association of IMP3 protein expression with disease recurrence, cancer-specific mortality, and all-cause mortality.
  
  
  CONCLUSIONS
  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, IMP3 expression 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.
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Lee
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, NY, USA; Inserm U955 Equipe 07, UPEC, Créteil, France; Department of Urology, Cochin Hospital, APHP, Paris Descartes University, Paris, France.
authors.forename: Evanguelos
authors.initials: E
authors.lastname: Xylinas
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, NY, USA; Department of Urology, University Hospital Basel, Basel, Switzerland.
authors.forename: Malte
authors.initials: M
authors.lastname: Rieken
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Francesca
authors.initials: F
authors.lastname: Khani
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna, Austria.
authors.forename: Tobias
authors.initials: T
authors.lastname: Klatte
authors.affiliation: Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
authors.affiliation: Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Karam
authors.affiliation: Department of Urology, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Alon Z
authors.initials: AZ
authors.lastname: Weizer
authors.affiliation: Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Raman
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna, Austria.
authors.forename: Mesut
authors.initials: M
authors.lastname: Remzi
authors.affiliation: Department of Pathology, University of Texas MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Guo
authors.affiliation: Department of Pathology, University of Rennes, Rennes, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rioux-Leclercq
authors.affiliation: Department of Pathology, Medical University of Vienna, Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Haitel
authors.affiliation: Department of Urology, Mannheim Medical Center, University of Heidelberg, Mannheim, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Bolenz
authors.affiliation: Department of Urology, University of Rennes, Rennes, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Bensalah
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Arthur I
authors.initials: AI
authors.lastname: Sagalowsky
authors.affiliation: Department of Urology, Vita-Salute University, Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Montorsi
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.affiliation: Department of Urology, Medical University of Vienna, Vienna, Austria. Electronic address: sfshariat@gmail.com.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
authors.affiliation: Department of Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Robinson
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
mesh_terms: D000368:Aged; D002277:Carcinoma / Q000737:chemistry* / Q000401:mortality* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000737:chemistry* / Q000401:mortality* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000737:chemistry*; D009392:Nephrectomy; D016601:RNA-Binding Proteins / Q000032:analysis*; D012189:Retrospective Studies; D015996:Survival Rate; D046888:Tissue Array Analysis; D014513:Ureter / Q000601:surgery; D014516:Ureteral Neoplasms / Q000737:chemistry* / Q000401:mortality* / Q000473:pathology; D019459:Urothelium
chemical_list: C498780:IGF2BP3 protein, human; D016601:RNA-Binding Proteins
keywords: Biomarker; Disease recurrence; IMP-3; Immunohistochemistry; Outcomes; Prognosis; Survival; Upper tract urothelial carcinoma