title: Nuclear localization of nuclear factor-kappaB p65 in primary prostate tumors is highly predictive of pelvic lymph node metastases.
abstract: OBJECTIVE
  Lymph node invasion (LNI) is associated with increased risk of prostate cancer progression. Unfortunately, pelvic lymph node dissections are fraught with a high rate of false-negative findings, emphasizing the need for highly accurate markers of LNI. Because nuclear factor-kappaB (NF-kappaB) is a candidate marker of prostate cancer progression, we tested the association between nuclear localization of NF-kappaB in radical prostatectomy specimens and the presence of LNI.
  
  
  METHODS
  NF-kappaB expression in radical prostatectomy specimens was assessed with a monoclonal NF-kappaB p65 antibody, in 20 patients with LNI and in 31 controls with no LNI and no biochemical relapse 5 years after radical prostatectomy. Univariate and multivariate logistic regression models were used. The accuracy of multivariate predictions with and without NF-kappaB was quantified with the area under the receiver operating characteristics curve and 200 bootstrap resamples were used to reduce overfit bias.
  
  
  RESULTS
  Univariate regression models showed a 7% increase in the odds of observing LNI for each 1% increase in NF-kappaB nuclear staining (odds ratio, 1.07; P = 0.003). In multivariate models, each 1% increase in NF-kappaB was associated with an 8% increase in the odds of LNI (odds ratio, 1.08; P = 0.03) and its statistical significance was only surpassed by the presence of seminal vesicle invasion (P = 0.003). Addition of NF-kappaB to all other predictors increased the accuracy of LNI prediction by 2.3% (from 84.8% to 87.1%; P < 0.001).
  
  
  CONCLUSIONS
  This is the first study that shows that the extent of nuclear localization of NF-kappaB in primary prostate tumors is highly accurately capable of predicting the probability of locoregional spread of prostate cancer.
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Institut du Cancer de Montréal, and the Department of Surgery/Urology, CHUM, University of Montréal, 1560 rue Sherbrooke est, Montréal, Québec, Canada.
authors.forename: Laurent
authors.initials: L
authors.lastname: Lessard
authors.forename: Pierre I
authors.initials: PI
authors.lastname: Karakiewicz
authors.forename: Pascale
authors.initials: P
authors.lastname: Bellon-Gagnon
authors.forename: Mona
authors.initials: M
authors.lastname: Alam-Fahmy
authors.forename: Hazem A
authors.initials: HA
authors.lastname: Ismail
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mes-Masson
authors.forename: Fred
authors.initials: F
authors.lastname: Saad
mesh_terms: D000368:Aged; D002467:Cell Nucleus / Q000378:metabolism; D006801:Humans; D008207:Lymphatic Metastasis / Q000175:diagnosis; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009367:Neoplasm Staging; D010388:Pelvis / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D021381:Protein Transport; D012669:Seminal Vesicles / Q000378:metabolism / Q000473:pathology
chemical_list: D016328:NF-kappa B; D017430:Prostate-Specific Antigen