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Br J Cancer ; 93(11): 1285-94, 2005 Nov 28.
Article in English | MEDLINE | ID: mdl-16278667

ABSTRACT

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.


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