Activation of nuclear factor-kappaB in human prostate carcinogenesis and association to biochemical relapse.
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.
Domingo-Domenech
J
J
Department of Medical Oncology, Hospital Clinic & Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.
Mellado
B
B
Ferrer
B
B
Truan
D
D
Codony-Servat
J
J
Sauleda
S
S
Alcover
J
J
Campo
E
E
Gascon
P
P
Rovira
A
A
Ross
J S
JS
Fernández
P L
PL
Albanell
J
J
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002467:Cell Nucleus; D002471:Cell Transformation, Neoplastic; D003593:Cytoplasm / Q000737:chemistry; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016328:NF-kappa B / Q000032:analysis / Q000096:biosynthesis* / Q000493:pharmacokinetics; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D017430:Prostate-Specific Antigen; D019048:Prostatic Intraepithelial Neoplasia / Q000235:genetics / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D012307:Risk Factors; D051996:Transcription Factor RelA / Q000032:analysis / Q000096:biosynthesis / Q000493:pharmacokinetics
D014408:Biomarkers, Tumor; D016328:NF-kappa B; D051996:Transcription Factor RelA; D017430:Prostate-Specific Antigen