Nuclear localization of NF-kappaB p65 in primary prostate tumors is predictive of pelvic lymph node metastases
10077 Background: Pelvic lymph node metastases are associated with a greater risk of prostate cancer recurrence and peripheral metastasis. Unfortunately, markers predictive of lymph node metastasis and/or recurrence after radical prostatectomy are limited and new molecular markers are needed to identify patients at higher risk of progression. NF-kB (p65) is a candidate molecular marker already associated with poor clinical outcomes such as biochemical recurrence and bone metastasis. We have also reported elevated nuclear p65 expression in prostate cancer lymph node metastasis. Pertinent to this issue, we tested whether the nuclear localization of p65 in radical prostatectomy specimens could predict the presence of lymph node metastases. Methods: Following informed consent, 51 patients who underwent radical prostatectomy were included in the study: 20 patients had lymph node metastasis at surgery and 31 patients had no evidence of lymph node metastasis and were used as the control group. All cases in the control group had no biochemical relapse 5 years following radical prostatectomy. NF-kB expression in prostate tumor sections was assessed by immunohistochemistry using a monoclonal NF-kB p65 antibody. The relation between nuclear p65 expression in primary tumors and lymph node metastasis was tested in univariate and multivariate Cox regression models. Results: Primary tumors of metastatic patients had an average of 21.25% of tumor cells with nuclear p65 expression as opposed to 9.42% of tumor cells of control patients (p=0.001). Univariate Cox regression demonstrated a 7.5% increased risk of having lymph node metastases for each percent increase in p65 nuclear staining (p=0.003). In the multivariate model, after controlling for pre-operative PSA (p=0.175), Gleason patterns (p=0.382), pathological stage (p=0.436), extracapsular extension (p=0.243) and seminal vesicle invasion (p=0.016), nuclear p65 was associated with an 8.8% increased risk for lymph node metastases (p=0.024). Conclusion: In univariate and multivariate analyses, p65 nuclear expression was strongly predictive of lymph node invasion. We propose that nuclear NF-kB (p65) may serve as a useful independent molecular marker for stratifying patients at risk for lymph node metastases. No significant financial relationships to disclose.