1. ¹Department of Medical Oncology and Laboratory of Experimental Oncology (ICMHO), Hospital Clinic & Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
2. ²Department of Pathology, Hospital Clinic & Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
3. ³Departments of Urology, Hospital Clinic & Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
4. ⁴Blood Bank Center, Hospital Vall d'Hebron, Barcelona, Spain
5. ⁵Department of Pathology and Laboratory Medicine, Albany Medical College, Albany, NY, USA
6. ⁶Millennium Pharmaceuticals, Inc., Cambridge, MA, USA

Correspondence: Dr J Albanell, Medical Oncology Department, Hospital del Mar, Passeig Maritim, 25-29, 08003 Barcelona, Spain. E-mail: jalbanell@imas.imim.es

Revised 20 July 2005; Accepted 3 October 2005; Published online 8 November 2005.

Abstract

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