Nuclear factor-κB nuclear localization is predictive of biochemical recurrence in patients with positive margin prostate cancer

Purpose: Radical prostatectomy (RP) patients with positive surgical margins are at increased risk for recurrence, emphasizing the need for prognostic markers to stratify probable outcome for optimal patient management decisions. We tested the hypothesis that nuclear localization of nuclear factor (NF)-kappaB, a transcription factor involved in the regulation of cell growth, angiogenesis, invasion, and apoptosis, is associated with an increased risk of biochemical recurrence after RP. Experimental Design: Analyses addressed data from 42 patients (age range, 52-72 years; mean age, 63.7 years) who exhibited positive surgical margins after RP. Immunohistochemical analysis of NF-kappaB (p65) was performed on the positive margin tissue. A nuclear staining cutoff of >5% was considered positive. The relation between nuclear NF-kappaB expression and biochemical recurrence (prostate-specific antigen >0.3 ng/mL and rising) after RP was tested in univariate and multivariate Cox regression models. Results: Biochemical recurrence was recorded in 23 patients (54.8%; median follow-up, 3.2 years). Univariate Cox regression demonstrated a 4.9-fold (95% confidence interval, 1.5-16.7; P = 0.01) higher rate of recurrence in men with NF-kappaB > 5%. In the multivariate model, after controlling for primary (P = 0.004) and secondary (P = 0.7) Gleason patterns, lymph node (P = 0.06) and seminal vesicle invasion (P = 0.2), and preoperative prostate-specific antigen (P = 0.009), NF-kappaB > 5% was associated with a 6.2-fold higher risk of biochemical recurrence (95% confidence interval, 1.7-23.5; P = 0.007). Conclusions: In univariate and multivariate analysis, NF-kappaB nuclear expression was strongly predictive of biochemical recurrence in patients with positive surgical margins after RP. We propose that nuclear NF-kappaB may serve as a useful independent molecular marker for stratifying patients at risk for recurrence.