title: Large-scale independent validation of the nuclear factor-kappa B p65 prognostic biomarker in prostate cancer.
abstract: OBJECTIVE
  Over the last decade, we and others have uncovered a robust association between the nuclear localisation of nuclear factor-kappa B (NF-κB) p65, prostate cancer (PCa) aggressiveness and biochemical recurrence (BCR). Our goal was to validate these results in a large independent cohort of PCa patients who underwent radical prostatectomy.
  
  
  METHODS
  A set of 1826 fully annotated prostate cancers treated by radical prostatectomy were analysed in a tissue microarray (TMA) format for NF-κB p65 immunohistochemistry-based protein expression. We performed standard Cox proportional hazard regression models for follow-up data, bootstrap procedure for model internal validation, Harrell's concordance index for model discrimination and graphical assessment of predicted versus actual outcomes for model calibration.
  
  
  RESULTS
  We observed a significant association between an increase in the nuclear frequency of NF-κB p65 and Gleason score (P<0.001), overall BCR (P<0.001) and development of metastases (P=0.001). NF-κB was found to be an independent predictor of BCR (P<0.001, Cox regression). However its contribution to the predictive accuracy of a multivariate model, which included preoperative PSA, Gleason score, extraprostatic extension, lymph node invasion, seminal vesicle involvement and surgical margin status, was modest.
  
  
  CONCLUSIONS
  Our study offers validating results linking NF-κB p65 with disease progression using a large cohort of European men. However, the contribution of NF-κB to a post-surgical predictive model appears modest. Further validating work should focus on evaluating the contribution of NF-κB p65 in pre-treatment models.
authors.affiliation: Centre de recherche du Centre hospitalier de l'Université de Montréal, Institut du cancer de Montréal, and Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
authors.forename: Philippe O
authors.initials: PO
authors.lastname: Gannon
authors.forename: Laurent
authors.initials: L
authors.lastname: Lessard
authors.forename: Louis-Mathieu
authors.initials: LM
authors.lastname: Stevens
authors.forename: Valérie
authors.initials: V
authors.lastname: Forest
authors.forename: Louis R
authors.initials: LR
authors.lastname: Bégin
authors.forename: Sarah
authors.initials: S
authors.lastname: Minner
authors.forename: Pierre
authors.initials: P
authors.lastname: Tennstedt
authors.forename: Thorsten
authors.initials: T
authors.lastname: Schlomm
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mes-Masson
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002467:Cell Nucleus / Q000378:metabolism; D015331:Cohort Studies; D018450:Disease Progression; D018572:Disease-Free Survival; D006801:Humans; D007150:Immunohistochemistry / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D016016:Proportional Hazards Models; D011467:Prostate / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D017430:Prostate-Specific Antigen / Q000032:analysis; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000378:metabolism* / Q000601:surgery; D012669:Seminal Vesicles / Q000378:metabolism / Q000473:pathology; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D046888:Tissue Array Analysis / Q000706:statistics & numerical data; D051996:Transcription Factor RelA / Q000032:analysis*
chemical_list: D014408:Biomarkers, Tumor; D051996:Transcription Factor RelA; D017430:Prostate-Specific Antigen