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

TY - JOUR

T1 - Large-scale independent validation of the nuclear factor-kappa B p65 prognostic biomarker in prostate cancer

AU - Gannon, Philippe O

AU - Lessard, Laurent

AU - Stevens, Louis-Mathieu

AU - Forest, Valérie

AU - Bégin, Louis R

AU - Minner, Sarah

AU - Tennstedt, Pierre

AU - Schlomm, Thorsten

AU - Mes-Masson, Anne-Marie

AU - Saad, Fred

N1 - Copyright © 2013 Elsevier Ltd. All rights reserved.

PY - 2013/7/1

Y1 - 2013/7/1

N2 - 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.

AB - 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.

KW - Aged

KW - Cell Nucleus

KW - Cohort Studies

KW - Disease Progression

KW - Disease-Free Survival

KW - Humans

KW - Immunohistochemistry

KW - Male

KW - Middle Aged

KW - Multivariate Analysis

KW - Neoplasm Recurrence, Local

KW - Prognosis

KW - Proportional Hazards Models

KW - Prostate

KW - Prostate-Specific Antigen

KW - Prostatectomy

KW - Prostatic Neoplasms

KW - Seminal Vesicles

KW - Sensitivity and Specificity

KW - Severity of Illness Index

KW - Tissue Array Analysis

KW - Transcription Factor RelA

KW - Tumor Markers, Biological

U2 - 10.1016/j.ejca.2013.02.026

DO - 10.1016/j.ejca.2013.02.026

M3 - SCORING: Journal article

C2 - 23541563

VL - 49

SP - 2441

EP - 2448

JO - EUR J CANCER

JF - EUR J CANCER

SN - 0959-8049

IS - 10

ER -