@article{7768fc8c8aba40c192fbfc13d7c9a465,
title = "Activation of nuclear factor-κB in human prostate carcinogenesis and association to biochemical relapse",
abstract = "Nuclear factor (NF)-κB/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-κB/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-κB active state. Nuclear localisation of NF-κB 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-κB was detected in 57 (66.3%) specimens, and nuclear NF-κB (activated) in 47 (54.7%). Nuclear and cytoplasmic NF-κB staining was not correlated (P=0.19). By univariate analysis, nuclear localisation of NF-κB 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-κB (P=0.002) were independent predictors of biochemical relapse. These results provide novel evidence for NF-κB/p65 nuclear translocation in the transition from PIN to prostate cancer. Our findings also indicate that nuclear localisation of NF-κB is an independent prognostic factor of biochemical relapse in prostate cancer.",
keywords = "Malignant transformation, NF-kappa;B, PSA, Prostate cancer, Transcription factor",
author = "J. Domingo-Domenech and B. Mellado and B. Ferrer and D. Truan and J. Codony-Servat and S. Sauleda and J. Alcover and E. Campo and P. Gascon and A. Rovira and Ross, {J. S.} and Fern{\'a}ndez, {P. L.} and J. Albanell",
note = "Funding Information: A total of 105 tissue specimens were selected for the present study following institutional guidelines. Paraffin blocks containing sufficient formalin-fixed tissue for marker analyses were obtained from six histologically normal prostate specimens, 13 cases of high grade PIN, and 86 PACs. The selected tissues were obtained from 86 radical prostatectomy specimens that were performed for biopsy-proven PAC at the Hospital Clinic of Barcelona. The normal prostatic tissues and high-grade PIN lesions came from the same patients with from whom prostate cancer was assessed. All clinical follow-up studies were also performed at the Hospital Clinic. This study was part of a project funded by the Spanish Science and Technology Ministry (MCYT; Grant Number SAF 2003–08181) that had been approved by the Ethics Committee of our institution. Funding Information: The work was funded by Spanish Science and Technology Ministry (MCYT); Grant number SAF 2003-08181. Spanish Health Ministry; Grant number FIS 01/1519. Red Tem{\'a}tica del C{\'a}ncer; Grant number C03/10 (Instituto de Salud Carlos III). Asociaci{\'o}n Espa{\~n}ola Contra el C{\'a}ncer (AECC)/Catalunya contra el C{\'a}ncer. JD-D was supported by a {\textquoteleft}Premi Fi de Residencia 2003–2004{\textquoteright} research grant from the Hospital Cl{\'i}nic of Barcelona (Spain). AR was supported by a {\textquoteleft}Beca de Investigaci{\'o}n Oncol{\'o}gica 2002{\textquoteright} fellowship from the Fundaci{\'o}n Cient{\'i}fica de la AECC. We thank Maria Calvo, from Serveis Cient{\'i}fico-T{\`e}cnics de la Universitat de Barcelona (UB), Facultat de Medicina, for her expert technical assistance in confocal microscopy. We also thank Fundacio Cellex (Barcelona, Spain) for a generous donation to set up the Experimental Oncology Laboratory.",
year = "2005",
month = nov,
day = "28",
doi = "10.1038/sj.bjc.6602851",
language = "English (US)",
volume = "93",
pages = "1285--1294",
journal = "British journal of cancer",
issn = "0007-0920",
publisher = "Nature Publishing Group",
number = "11",
}