title: Survivin is not an independent prognostic factor for patients with upper tract urothelial carcinoma: a multi-institutional study.
abstract: OBJECTIVE
  Several small single-center studies have reported conflicting results on the prognostic value of survivin expression in upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy. We attempted to validate the prognostic utility of survivin using a large multi-institutional cohort.
  
  
  METHODS
  Survivin expression was evaluated by immunohistochemistry in tumor tissue from 732 patients with unilateral, sporadic UTUC treated with radical nephroureterectomy between 1990 and 2008 at 7 centers. Survivin expression was considered altered when at least 10% of the tumor cells stained positive. Associations of altered survivin expression with recurrence-free survival (RFS) and cancer-specific survival (CSS) were evaluated using Cox proportional hazards regression models.
  
  
  RESULTS
  Altered survivin expression was observed in 288 (39.3%) tumors and was associated with more advanced pathological tumor stages (P<0.001), lymph node metastases (P<0.001), lymphovascular invasion (P<0.001), tumor necrosis (P = 0.027), and tumor architecture (P<0.001). Median follow-up was 35 (16-64) months. There were 191 (25.4%) patients who experienced disease recurrence, and 165 patients (21.9%) died of the disease. In the univariable analysis, altered survivin expression was significantly associated with worse RFS and CSS (each P<0.001); however, altered survivin expression did not achieve independent predictive status on multivariable models (P = 0.24 and P = 0.53). Similarly, survivin was not independently associated with outcomes in subgroup analyses, including patients with high-grade tumors.
  
  
  CONCLUSIONS
  In UTUC, altered survivin expression is associated with worse clinicopathological features and worse RFS and CSS. However, it does not appear to be independently associated with cancer outcomes when considering standard prognostic factors.
authors.affiliation: Department of Urology, Medical University Vienna, General Hospital, Vienna, Austria; Department of Urology, Rennes University Hospital, Rennes, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Mathieu
authors.affiliation: Department of Urology, Medical University Vienna, General Hospital, Vienna, Austria.
authors.forename: Tobias
authors.initials: T
authors.lastname: Klatte
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX.
authors.forename: Vitaly
authors.initials: V
authors.lastname: Margulis
authors.affiliation: Department of Urology, MD Anderson Cancer Center, Houston, TX.
authors.forename: Jose A
authors.initials: JA
authors.lastname: Karam
authors.affiliation: Academic Department of Urology, La Pitié-Salpetrière Hospital, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Pierre et Marie Curie, University Paris 6, Paris, France.
authors.forename: Morgan
authors.initials: M
authors.lastname: Rouprêt
authors.affiliation: Department of Urology, Medical University Vienna, General Hospital, 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, Medical University Vienna, General Hospital, Vienna, Austria.
authors.forename: Harun
authors.initials: H
authors.lastname: Fajkovic
authors.affiliation: Department of Urology, MD Anderson Cancer Center, Houston, TX.
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Wood
authors.affiliation: Department of Urology, University of Michigan Cancer Center, Ann Arbor, MI.
authors.forename: Alon Z
authors.initials: AZ
authors.lastname: Weizer
authors.affiliation: Division of Urology, Penn State Milton S. Hershey Medical Center, Hershey, PA.
authors.forename: Jay D
authors.initials: JD
authors.lastname: Raman
authors.affiliation: Department of Urology, Medical University Vienna, General Hospital, 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, Medical University Vienna, Vienna, Austria.
authors.forename: Andrea
authors.initials: A
authors.lastname: Haitel
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.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
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, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Kluth
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, NY.
authors.forename: Douglas S
authors.initials: DS
authors.lastname: Scherr
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York, NY; Department of Pathology, Weill Cornell Medical College, New York, NY.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Robinson
authors.affiliation: Department of Urology, Medical University Vienna, General Hospital, Vienna, Austria; Department of Urology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX; Department of Urology, Weill Cornell Medical College, New York, NY. Electronic address: shahrokh.shariat@meduniwien.ac.at.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002295:Carcinoma, Transitional Cell / Q000378:metabolism / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D009367:Neoplasm Staging; D009392:Nephrectomy; D011379:Prognosis; D015996:Survival Rate; D000077022:Survivin; D014571:Urologic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology* / Q000601:surgery
chemical_list: C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin
keywords: Carcinoma; Death; Recurrence; Survivin; Urothelium