Nuclear localization of nuclear factor-κB p65 in primary prostate tumors is highly predictive of pelvic lymph node metastases

Purpose: 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-kappa B (NF-kappa B) is a candidate marker of prostate cancer progression, we tested the association between nuclear localization of NF-kappa B in radical prostatectomy specimens and the presence of LNI. Experimental Design: NF-kappa B expression in radical prostatectomy specimens was assessed with a monoclonal NF-kappa B 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-kappa B 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-kappa B nuclear staining (odds ratio, 1.07; P = 0.003). In multivariate models, each 1% increase in NF-kappa B 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-kappa B to all other predictors increased the accuracy of LNI prediction by 2.3% (from 84.8% to 87.1%; P < 0.001). Conclusion: This is the first study that shows that the extent of nuclear localization of NF-kappa B in primary prostate tumors is highly accurately capable of predicting the probability of locoregional spread of prostate cancer.