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

Authors' Affiliations: Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Institut du Cancer de Montréal, and the Department of Surgery/Urology, CHUM, University of Montréal, Montréal, Québec, Canada

Requests for reprints: Fred Saad, Centre Hospitalier de l'Université de Montréal, 1560 rue Sherbrooke est, Montréal, Québec, Canada H2L 4M1. Phone: 514-890-8000-27466; Fax: 514-412-7620; E-mail: fred.saad.chum{at}ssss.gouv.qc.ca.

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-B (NF-B) is a candidate marker of prostate cancer progression, we tested the association between nuclear localization of NF-B in radical prostatectomy specimens and the presence of LNI.

Experimental Design: NF-B expression in radical prostatectomy specimens was assessed with a monoclonal NF-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-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-B nuclear staining (odds ratio, 1.07; P = 0.003). In multivariate models, each 1% increase in NF-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-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-B in primary prostate tumors is highly accurately capable of predicting the probability of locoregional spread of prostate cancer.

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