title: ERCC1 as a Prognostic and Predictive Biomarker for Urothelial Carcinoma of the Bladder following Radical Cystectomy.
abstract: OBJECTIVE
  ERCC1 is the key enzyme of the nucleotide excision repair pathway, which maintains genomic stability. ERCC1 has been proposed as a prognostic and predictive biomarker for patients with urothelial carcinoma of the bladder but there are limited data on patients after radical cystectomy.
  
  
  METHODS
  ERCC1 was evaluated by immunohistochemistry in radical cystectomy specimens of 432 patients. Associations with disease-free and cancer specific survival, and the effect of adjuvant cisplatin based chemotherapy were assessed. Further, ERCC1 mRNA expression and in vitro sensitivity to cisplatin were correlated in 25 bladder urothelial carcinoma cell lines.
  
  
  RESULTS
  ERCC1 was expressed in 308 tumors (71.3%). There was no association with clinicopathological variables (each p >0.3). Median postoperative followup was 128 months. On multivariable analyses patients with ERCC1 positive tumors had significantly better disease-free survival (HR 0.70, p = 0.028) and cancer specific survival (HR 0.70, p = 0.032) than those with ERCC1 negative tumors. Discrimination of the multivariable models increased by 0.7% to 0.9% following the inclusion of ERCC1. There was no modification of the effect of adjuvant cisplatin based combination chemotherapy by ERCC1 status (p = 0.38 and 0.88, respectively). There was also no correlation between ERCC1 and sensitivity to cisplatin in vitro (R(2) = 0.02, p = 0.46).
  
  
  CONCLUSIONS
  ERCC1 may be a prognostic biomarker for urothelial carcinoma of the bladder. Patients with ERCC1 positive tumors may have better survival than those with ERCC1 negative tumors. However, the efficacy of adjuvant cisplatin based chemotherapy appears to be unrelated to ERCC1 status.
authors.affiliation: Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Tobias
authors.initials: T
authors.lastname: Klatte
authors.affiliation: Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Seitz
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, New York; Department of Urology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Rink
authors.affiliation: Academic Department of Urology, Pitié-Salpétrière Hospital, Paris, France; UPMC University of Paris 06, GRC5, Oncotype-Uro, Institut Universitaire de Cancérologie, Paris, France.
authors.forename: Morgan
authors.initials: M
authors.lastname: Rouprêt
authors.affiliation: Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, New York; Department of Urology, Cochin Hospital, Paris Descartes University, Paris, France.
authors.forename: Evanguelos
authors.initials: E
authors.lastname: Xylinas
authors.affiliation: Cancer Prognostics and Health Outcomes Unit, University of Montreal Health Centre, Montreal, Quebec, Canada.
authors.forename: Pierre
authors.initials: P
authors.lastname: Karakiewicz
authors.affiliation: Clinical Institute of Pathology, Medical University of Vienna, Vienna General Hospital, Vienna, Austria.
authors.forename: Martin
authors.initials: M
authors.lastname: Susani
authors.affiliation: Department of Urology, Comprehensive Cancer Center, Medical University of Vienna, Vienna General Hospital, Vienna, Austria; Department of Urology, Weill Cornell Medical College, New York-Presbyterian Hospital, New York, New York; Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas. Electronic address: sfshariat@gmail.com.
authors.forename: Shahrokh F
authors.initials: SF
authors.lastname: Shariat
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D045744:Cell Line, Tumor; D015653:Cystectomy; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics*; D018450:Disease Progression; D004720:Endonucleases / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D011379:Prognosis; D012334:RNA, Neoplasm / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D012334:RNA, Neoplasm; C071447:ERCC1 protein, human; D004720:Endonucleases
keywords: ERCC1 protein; biological markers; cisplatin; human; prognosis; urinary bladder neoplasms