Large-scale independent validation of the nuclear factor-kappa B p65 prognostic biomarker in prostate cancer

Eur J Cancer. 2013 Jul;49(10):2441-8. doi: 10.1016/j.ejca.2013.02.026. Epub 2013 Mar 28.


Purpose: 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.

Experimental design: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis*
  • Cell Nucleus / metabolism
  • Cohort Studies
  • Disease Progression
  • Disease-Free Survival
  • Humans
  • Immunohistochemistry / statistics & numerical data
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Recurrence, Local
  • Prognosis
  • Proportional Hazards Models
  • Prostate / metabolism*
  • Prostate / pathology
  • Prostate / surgery
  • Prostate-Specific Antigen / analysis
  • Prostatectomy / methods
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / surgery
  • Seminal Vesicles / metabolism
  • Seminal Vesicles / pathology
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Tissue Array Analysis / statistics & numerical data
  • Transcription Factor RelA / analysis*


  • Biomarkers, Tumor
  • Transcription Factor RelA
  • Prostate-Specific Antigen