학술논문

Activation of nuclear factor-kappaB in human prostate carcinogenesis and association to biochemical relapse.
Document Type
Journal Article
Source
British Journal of Cancer. 11/28/2005, Vol. 93 Issue 11, p1285-1294. 10p.
Subject
*PROTEIN analysis
*ADENOCARCINOMA
*PROTEINS
*RESEARCH
*MULTIVARIATE analysis
*IMMUNOHISTOCHEMISTRY
*RESEARCH methodology
*NF-kappa B
*NEOPLASTIC cell transformation
*PROGNOSIS
*CANCER relapse
*EVALUATION research
*CELL nuclei
*COMPARATIVE studies
*GENE expression profiling
*PROSTATE-specific antigen
*PROSTATE tumors
*CARCINOMA in situ
*CYTOPLASM
Language
ISSN
0007-0920
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. [ABSTRACT FROM AUTHOR]