Nuclear Localization of Nuclear Factor-κB p65 in Primary Prostate Tumors Is Highly Predictive of Pelvic Lymph Node Metastases

Abstract

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. 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. 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). 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.