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

J. Domingo-Domenech, B. Mellado, B. Ferrer, D. Truan, J. Codony-Servat, S. Sauleda, J. Alcover, E. Campo, P. Gascon, A. Rovira, J. S. Ross, P. L. Fernández, J. Albanell

Research output: Contribution to journalArticlepeer-review

Abstract

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

Original languageEnglish (US)
Pages (from-to)1285-1294
Number of pages10
JournalBritish journal of cancer
Volume93
Issue number11
DOIs
StatePublished - Nov 28 2005

Keywords

  • Malignant transformation
  • NF-kappa;B
  • Prostate cancer
  • PSA
  • Transcription factor

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint

Dive into the research topics of 'Activation of nuclear factor-κB in human prostate carcinogenesis and association to biochemical relapse'. Together they form a unique fingerprint.

Cite this