Activation of nuclear factor-kappa B 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, JS Ross, PL Fernandez, J Albanell

Research output: Contribution to journalArticleResearchpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)1285-1294
Number of pages10
JournalBr. J. Cancer
Volume93
Issue number11
DOIs
Publication statusPublished - 28 Nov 2005

Keywords

  • prostate cancer
  • NF-kappa B
  • transcription factor
  • malignant transformation
  • PSA
  • NECROSIS-FACTOR-ALPHA
  • CANCER CELLS
  • CONSTITUTIVE ACTIVATION
  • INTRAEPITHELIAL NEOPLASIA
  • INTERLEUKIN-6 EXPRESSION
  • TRANSCRIPTION FACTOR
  • CARCINOMA-CELLS
  • KINASE-ALPHA
  • APOPTOSIS
  • INHIBITION

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