Activation of nuclear factor-κB in human prostate carcinogenesis and association to biochemical relapse

Nuclear factor (NF)-kappa B/p65 regulates the transcription of a wide variety of genes involved in cell survival, invasion and metastasis. We characterised by immunohistochemistry the expression of NF-kappa B/p65 protein in six histologically normal prostate, 13 high-grade prostatic intraepithelial neoplasia (PIN) and 86 prostate adenocarcinoma specimens. Nuclear localisation of p65 was used as a measure of NF-kappa B active state. Nuclear localisation of NF-kappa B was only seen in scattered basal cells in normal prostate glands. Prostatic intraepithelial neoplasias exhibited diffuse and strong cytoplasmic staining but no nuclear staining. In prostate adenocarcinomas, cytoplasmic NF-kB was detected in 57 (66.3%) specimens, and nuclear NF-kappa B (activated) in 47 (54.7%). Nuclear and cytoplasmic NF-kappa B staining was not correlated (P = 0.19). By univariate analysis, nuclear localisation of NF-kappa B was associated with biochemical relapse (P = 0.0009; log- rank test) while cytoplasmic expression did not. On multivariate analysis, serum preoperative prostate specific antigen (P = 0.02), Gleason score (P = 0.03) and nuclear NF-kappa B (P = 0.002) were independent predictors of biochemical relapse. These results provide novel evidence for NF-kappa B/p65 nuclear translocation in the transition from PIN to prostate cancer. Our findings also indicate that nuclear localisation of NF-kappa B is an independent prognostic factor of biochemical relapse in prostate cancer.