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

Br J Cancer. 2005 Nov 28;93(11):1285-94. doi: 10.1038/sj.bjc.6602851.


Nuclear factor (NF)-kappaB/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-kappaB/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-kappaB active state. Nuclear localisation of NF-kappaB 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-kappaB was detected in 57 (66.3%) specimens, and nuclear NF-kappaB (activated) in 47 (54.7%). Nuclear and cytoplasmic NF-kappaB staining was not correlated (P=0.19). By univariate analysis, nuclear localisation of NF-kappaB 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-kappaB (P=0.002) were independent predictors of biochemical relapse. These results provide novel evidence for NF-kappaB/p65 nuclear translocation in the transition from PIN to prostate cancer. Our findings also indicate that nuclear localisation of NF-kappaB is an independent prognostic factor of biochemical relapse in prostate cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology*
  • Aged
  • Biomarkers, Tumor / analysis
  • Cell Nucleus
  • Cell Transformation, Neoplastic*
  • Cytoplasm / chemistry
  • Gene Expression Profiling
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Multivariate Analysis
  • NF-kappa B / analysis
  • NF-kappa B / biosynthesis*
  • NF-kappa B / pharmacokinetics
  • Neoplasm Recurrence, Local
  • Prognosis
  • Prostate-Specific Antigen
  • Prostatic Intraepithelial Neoplasia / genetics
  • Prostatic Intraepithelial Neoplasia / pathology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*
  • Risk Factors
  • Transcription Factor RelA / analysis
  • Transcription Factor RelA / biosynthesis
  • Transcription Factor RelA / pharmacokinetics


  • Biomarkers, Tumor
  • NF-kappa B
  • Transcription Factor RelA
  • Prostate-Specific Antigen