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.
Written by:
Gannon PO, Lessard L, Stevens LM, Forest V, Bégin LR, Minner S, Tennstedt P, Schlomm T, Mes-Masson AM, Saad F. Are you the author?
Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Institut du cancer de Montréal, and Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
Reference: Eur J Cancer. 2013 Mar 27. pii: S0959-8049(13)00158-5.
doi: 10.1016/j.ejca.2013.02.026
PubMed Abstract
PMID: 23541563
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