title: Utility of biomarkers in the prediction of oncologic outcome after radical cystectomy for squamous cell carcinoma.
abstract: OBJECTIVE
  We evaluated the association of multiple biomarkers with clinical outcomes in patients treated with radical cystectomy for squamous cell carcinoma of the bladder to identify the best prognostic panel of markers.
  
  
  METHODS
  Immunohistochemistry for 14 biomarkers was performed on tissue microarray sections of 151 radical cystectomy specimens showing squamous cell carcinoma. Biomarker alterations, pathological features and oncologic outcomes were evaluated. The panel of biomarkers that best predicted the oncologic outcome was determined. Outcomes were stratified based on a prognostic score according to the number of altered biomarkers. The accuracy of oncologic outcome prediction was evaluated by ROC curves.
  
  
  RESULTS
  The study included 151 patients. Pathological stage was T2 in 50%, T3 in 38%, T1 in 6% and T4 in 6% of patients. Median followup was 63.2 months. The best prognostic panel of markers included COX-2, FGF-2, p53, Bax and EGFR. On multivariate Cox regression analysis a prognostic score based on marker alterations was an independent predictor of intermediate and high risk of disease recurrence (HR 3.2, p = 0.008 and HR 15.5, p ≤ 0.001) and bladder cancer specific mortality (HR 5.2, p = 0.009 and HR 19.4, p ≤ 0.001, respectively). A multivariate prognostic model incorporating the prognostic score demonstrated significantly better performance to predict the outcome compared to clinicopathological parameters only (0.78 vs 0.64).
  
  
  CONCLUSIONS
  Biomarkers have significant potential to predict the outcome of radical cystectomy for squamous cell carcinoma. An increased number of altered markers may identify patients at high risk who might benefit from multimodal treatment approaches.
authors.affiliation: Department of Urology, University of California-Irvine, Irvine, California; Department of Urology and Nephrology Center, Mansoura University, Mansoura, Egypt. Electronic address: ryaacoub@uci.edu.
authors.forename: Ramy F
authors.initials: RF
authors.lastname: Youssef
authors.affiliation: Department of Helios Klinikum Wuppertal, University Witten-Herdecke, Germany; Department of Urology, Baylor College of Medicine, Houston, Texas.
authors.forename: Friedrich-Carl
authors.initials: FC
authors.lastname: von Rundstedt
authors.affiliation: Department of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Payal
authors.initials: P
authors.lastname: Kapur
authors.affiliation: Department of Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Mosbah
authors.affiliation: Department of Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
authors.forename: Hassan
authors.initials: H
authors.lastname: Abol-Enein
authors.affiliation: Department of Urology and Nephrology Center, Mansoura University, Mansoura, Egypt.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Ghoneim
authors.affiliation: Department of Urology, University of Texas Southwestern Medical Center, Dallas, Texas.
authors.forename: Yair
authors.initials: Y
authors.lastname: Lotan
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000737:chemistry* / Q000601:surgery*; D015653:Cystectomy / Q000379:methods; D006801:Humans; D008875:Middle Aged; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000601:surgery*
chemical_list: D015415:Biomarkers
keywords: biological markers; carcinoma; cystectomy; schistosomiasis; squamous cell; urinary bladder