NF-κB nuclear localization and its prognostic significance in prostate cancer

OBJECTIVE To detect the subcellular localization of NF-kappaB (p65) in human prostate cancer tissues of different histological grades, and to test whether NF-kappaB localization alone, or combined with the histological grade, can be used to predict patient outcome. PATIENTS AND METHODS Prostate cancer tissues were obtained from radical prostatectomy specimens; the histological grade was determined using the Gleason grading system. Clinical outcomes were defined as good (5-year disease-free survival with undetectable levels of prostate specific antigen) or poor (progression to bone metastases). The subcellular localization of NF-kappaB was visualized by immunohistochemistry using an anti-p65 antibody. RESULTS The NF-kappaB subcellular localization was initially assessed in 45 specimens; in these samples a nuclear localization of NF-kappaB was specific to cancer tissues, but did not correlate with the Gleason score (P = 0.089). NF-kappaB was then assessed as a prognostic marker to complement Gleason score in predicting cancer progression. Tumour tissues from 30 men with a known clinical outcome were included; 10 of 17 patients who had a poor outcome were positive for NF-kappaB nuclear staining, whereas only two of 13 with a good outcome were positive (P = 0.026). When NF-kappaB subcellular localization and Gleason score were combined, two risk categories of progression were defined. Eleven of 13 specimens from those with a good outcome were in the low-risk category (Gleason 2-4 or Gleason 5-7 with negative nuclear NF-kappaB) and 12 of 17 in the poor outcome group were in the high-risk category (Gleason 8-10 or Gleason 5-7 with positive nuclear NF-kappaB; P = 0.004). CONCLUSION NF-kappaB is detectable in the nucleus in prostate cancer tissues and positivity can be used to help predict patient outcome. Multivariate analyses using other clinical and molecular variables are underway, and will validate the usefulness of NF-kappaB as a prognostic factor.