title: Prognostic role of decreased E-cadherin expression in patients with upper tract urothelial carcinoma: a multi-institutional study.
abstract: OBJECTIVE
  To assess the role of E-cadherin as prognostic biomarker in upper tract urothelial carcinoma (UTUC) in a large multi-institutional cohort of patients.
  
  
  METHODS
  Immunohistochemistry technique was used to evaluate E-cadherin expression in 678 patients with unilateral, sporadic UTUC treated with RNU. E-cadherin expression was considered decreased if 10 % or more cells had decreased expression (<90 %).
  
  
  RESULTS
  Decreased E-cadherin expression was observed in 353 patients (52.1 %) and was associated with advanced pathological stage (P < 0.001), higher grade (P < 0.001), lymph node metastasis (P = 0.006), lymphovascular invasion (P < 0.001), concomitant carcinoma in situ (P < 0.001), multifocality (P = 0.004), tumor necrosis (P = 0.020) and sessile architecture (P < 0.001). Within a median follow-up of 30 months (interquartile range 15-57), 171 patients (25.4 %) experienced disease recurrence and 150 (21.9 %) died from UTUC. In univariable analyses, decreased E-cadherin expression was significantly associated with worse recurrence-free survival (P < 0.001) and cancer-specific survival CSS (P = 0.006); however, in multivariable analyses, it was not (P = 0.74 and 0.84, respectively). The lack of independent prognostic value of E-cadherin remained true in all subgroup analyses.
  
  
  CONCLUSIONS
  In UTUC patients treated with RNU, decreased E-cadherin expression is associated with features of biologically and clinically aggressive disease and worse outcome in univariable, but not multivariable, analyses. If E-cadherin's association with factors of advanced disease is confirmed on UTUC biopsy specimens, it could be used to help in the clinical decision-making regarding kidney-sparing approaches and/or neo-adjuvant chemotherapy.
authors.affiliation: Department of Urology, A. C. Camargo Hospital, São Paulo, Brazil.
authors.forename: Ricardo L
authors.initials: RL
authors.lastname: Favaretto
authors.affiliation: Department of Urology and Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Währinger Gürtel 18-20, 1090, Vienna, Austria.
authors.forename: Atessa
authors.initials: A
authors.lastname: Bahadori
authors.affiliation: Department of Urology, A. C. Camargo Hospital, São Paulo, Brazil.|Department of Urology, Rennes University Hospital, Rennes, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Mathieu
authors.affiliation: Department of Pathology, Medical University Vienna, Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Haitel
authors.affiliation: Department of Urology and Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Währinger Gürtel 18-20, 1090, Vienna, Austria.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Grubmüller
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
authors.affiliation: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Karam
authors.affiliation: Academic Department of Urology, Faculté de Médecine Pierre et Marie Curie, La Pitié-Salpetrière Hospital, Assistance Publique-Hôpitaux de Paris, University Paris 6, Paris, France.
authors.forename: Morgan
authors.initials: M
authors.lastname: Rouprêt
authors.affiliation: Department of Urology and Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Währinger Gürtel 18-20, 1090, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Seitz
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Canada.
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.affiliation: Department of Urology, A. C. Camargo Hospital, São Paulo, Brazil.
authors.forename: Isabela W
authors.initials: IW
authors.lastname: Cunha
authors.affiliation: Department of Urology, A. C. Camargo Hospital, São Paulo, Brazil.
authors.forename: Stenio C
authors.initials: SC
authors.lastname: Zequi
authors.affiliation: Department of Urology, MD Anderson Cancer Center, Houston, TX, USA.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
authors.affiliation: Department of Urology, University of Michigan Cancer Center, 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 and Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Währinger Gürtel 18-20, 1090, Vienna, Austria.
authors.forename: Mesut
authors.initials: M
authors.lastname: Remzi
authors.affiliation: Department of Pathology, Rennes University Hospital, Rennes, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rioux-Leclercq
authors.affiliation: Department of Pathology, Rennes University Hospital, Rennes, France.
authors.forename: Solene
authors.initials: S
authors.lastname: Jacquet-Kammerer
authors.affiliation: Department of Urology, Rennes University Hospital, Rennes, France.
authors.forename: Karim
authors.initials: K
authors.lastname: Bensalah
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
authors.affiliation: Department of Urology, University Hospital Basel, Basel, Switzerland.
authors.forename: Alexander
authors.initials: A
authors.lastname: Bachmann
authors.affiliation: Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Rink
authors.affiliation: Department of Urology, Vita Salute San Raffaele University, Milan, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Briganti
authors.affiliation: Department of Urology and Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Währinger Gürtel 18-20, 1090, Vienna, Austria. sfshariat@gmail.com.|Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX, USA. sfshariat@gmail.com.|Department of Urology, Weill Cornell Medical College, New York, NY, USA. sfshariat@gmail.com.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
mesh_terms: D000368:Aged; D015703:Antigens, CD; D015820:Cadherins / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009378:Neoplasms, Multiple Primary / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D012189:Retrospective Studies; D014516:Ureteral Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins
keywords: Carcinoma; E-cadherin; Prediction; Prognosis; Recurrence; Survival; Urothelium