Molecular Diagnostics

British Journal of Cancer (2005) 93, 1019–1023. doi:10.1038/sj.bjc.6602796 www.bjcancer.com
Published online 4 October 2005

Nuclear localisation of nuclear factor-kappaB transcription factors in prostate cancer: an immunohistochemical study

L Lessard1, L R Bégin2, M E Gleave3, A-M Mes-Masson1,4 and F Saad1,5

  1. 1Centre de recherche du CHUM, and Institut du cancer de Montréal, 1560 Sherbrooke Est, Montréal, Québec, Canada H2L 4M1
  2. 2Service d'anatomopathologie, Hôpital du Sacré-Co eligur de Montréal, 5400 boul. Gouin Ouest, Montréal, Québec, Canada H4J 1C5
  3. 3The Prostate Centre, Vancouver General Hospital, University of British Columbia, D-9, 2733 Heather Street, Vancouver, British Columbia, Canada V5Z 3J5
  4. 4Département de médecine, Université de Montréal, Québec, Canada
  5. 5Département de chirurgie (urologie), CHUM-Notre-Dame, 1560 Sherbrooke Est, Montréal, Québec, Canada H2L 4M1

Correspondence: Dr F Saad, Département d'urologie, Centre Hospitalier de l'Université de Montréal – Hôpital Notre-Dame, 1560 rue Sherbrooke E, Montréal, Québec, Canada H2L 4M1. E-mail: Fred.Saad.CHUM@ssss.gouv.qc.ca

Received 5 May 2005; Revised 9 August 2005; Accepted 23 August 2005; Published online 4 October 2005.

Top

Abstract

Several reports suggest that the canonical nuclear factor-kappaB (NF-kappaB) pathway is constitutively activated in a subset of prostate cancer cells. However, except for RelA (p65), little is known about the status of NF-kappaB transcription factors in prostate cancer tissues. To clarify the status of NF-kappaB subunits, we analysed the expression and subcellular localisation of RelA, RelB, c-Rel, p50, and p52 on tissue array sections containing respectively 344, 346, 369, 343, and 344 cores from 75 patients. The subcellular localisation of NF-kappaB factors was tested against relevant clinical parameters (preoperative prostate-specific antigen, pathological stage, and postoperative Gleason grade). With the exception of c-Rel, each subunit was detected in the nucleus of cancer cells: significant nuclear expression of RelB, RelA, p52, and p50 was seen in 26.6, 15.6, 10.7, and 10.5% of cores, respectively. Surprisingly, cores expressing both nuclear RelA and p50 canonical pathway proteins were less frequently observed than cores expressing other subunit combinations such as RelB–p52 and RelA–RelB. In addition, the nuclear localisation of RelB correlated with patient's Gleason scores (Spearman correlation: 0.167; P=0.018). The nuclear localisation of both canonical and noncanonical NF-kappaB subunits in prostate cancer cells suggests for the first time that different NF-kappaB pathways and dimers may be activated in the progression of the disease.

Keywords:

prostate cancer, NF-kappaB, immunohistochemistry, tissue microarray, Gleason grade