Limits...
Activation of nuclear factor-kappaB in human prostate carcinogenesis and association to biochemical relapse.

Domingo-Domenech J, Mellado B, Ferrer B, Truan D, Codony-Servat J, Sauleda S, Alcover J, Campo E, Gascon P, Rovira A, Ross JS, Fernández PL, Albanell J - Br. J. Cancer (2005)

Bottom Line: By univariate analysis, nuclear localisation of NF-kappaB was associated with biochemical relapse (P=0.0009; log-rank test) while cytoplasmic expression did not.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Hospital Clinic & Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

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.

Show MeSH

Related in: MedlinePlus

Upper panels, Kaplan–Meier survival curves for cytoplasmic and nuclear NF-κB expression in prostate adenocarcinomas. (A) No association between NF-κB cytoplasmic expression and biochemical disease recurrence was detected (P=0.74). (B) Nuclear expression of NF-κB was associated to the chance of biochemical disease-free survival. Patients with nuclear NF-κB had a higher risk of biochemical disease recurrence compared with those whose primary tumours did not have nuclear NF-κB (P=0.0009). Lower panels, Kaplan–Meier survival curves for NF-κB nuclear expression combined with presurgical serum prostate specific antigen (PSA) levels and Gleason score. (C) Patients with positive nuclear NF-κB expression and both (PSA⩾10 ng ml−1 and gleason ⩾7) adverse prognostic factors had a greater chance of biochemical disease recurrence than those who presented one (PSA⩾10 ng ml−1 or gleason ⩾7) or no (PSA⩽10 ng ml−1 and gleason⩽6) adverse independent prognostic factors (P=0.0032). (D) Patients with negative nuclear NF-κB expression, PSA<10 ng ml−1 and Gleason⩽6 presented had a better prognosis compared to patients with negative nuclear NF-κB expression and one (PSA⩾10 ng ml−1 or gleason⩾7) or both (PSA⩾10 ng ml−1 and gleason⩾7) adverse independent prognostic factors (P=0.046).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2361509&req=5

fig3: Upper panels, Kaplan–Meier survival curves for cytoplasmic and nuclear NF-κB expression in prostate adenocarcinomas. (A) No association between NF-κB cytoplasmic expression and biochemical disease recurrence was detected (P=0.74). (B) Nuclear expression of NF-κB was associated to the chance of biochemical disease-free survival. Patients with nuclear NF-κB had a higher risk of biochemical disease recurrence compared with those whose primary tumours did not have nuclear NF-κB (P=0.0009). Lower panels, Kaplan–Meier survival curves for NF-κB nuclear expression combined with presurgical serum prostate specific antigen (PSA) levels and Gleason score. (C) Patients with positive nuclear NF-κB expression and both (PSA⩾10 ng ml−1 and gleason ⩾7) adverse prognostic factors had a greater chance of biochemical disease recurrence than those who presented one (PSA⩾10 ng ml−1 or gleason ⩾7) or no (PSA⩽10 ng ml−1 and gleason⩽6) adverse independent prognostic factors (P=0.0032). (D) Patients with negative nuclear NF-κB expression, PSA<10 ng ml−1 and Gleason⩽6 presented had a better prognosis compared to patients with negative nuclear NF-κB expression and one (PSA⩾10 ng ml−1 or gleason⩾7) or both (PSA⩾10 ng ml−1 and gleason⩾7) adverse independent prognostic factors (P=0.046).

Mentions: The relationship between NF-κB expression and the risk of biochemical relapse was assessed using Kaplan–Meier disease outcome analysis. Using a bimodal approach, the presence or absence of NF-κB cytoplasmic staining was not associated with the risk of biochemical relapse of the disease (Figure 3A; log-rank test, P=0.74). Using a semiquantitative scoring assessment approach (0, +, ++, +++), cytoplasmic NF-κB expression was similarly not significantly associated with the risk of biochemical relapse (data not shown).


Activation of nuclear factor-kappaB in human prostate carcinogenesis and association to biochemical relapse.

Domingo-Domenech J, Mellado B, Ferrer B, Truan D, Codony-Servat J, Sauleda S, Alcover J, Campo E, Gascon P, Rovira A, Ross JS, Fernández PL, Albanell J - Br. J. Cancer (2005)

Upper panels, Kaplan–Meier survival curves for cytoplasmic and nuclear NF-κB expression in prostate adenocarcinomas. (A) No association between NF-κB cytoplasmic expression and biochemical disease recurrence was detected (P=0.74). (B) Nuclear expression of NF-κB was associated to the chance of biochemical disease-free survival. Patients with nuclear NF-κB had a higher risk of biochemical disease recurrence compared with those whose primary tumours did not have nuclear NF-κB (P=0.0009). Lower panels, Kaplan–Meier survival curves for NF-κB nuclear expression combined with presurgical serum prostate specific antigen (PSA) levels and Gleason score. (C) Patients with positive nuclear NF-κB expression and both (PSA⩾10 ng ml−1 and gleason ⩾7) adverse prognostic factors had a greater chance of biochemical disease recurrence than those who presented one (PSA⩾10 ng ml−1 or gleason ⩾7) or no (PSA⩽10 ng ml−1 and gleason⩽6) adverse independent prognostic factors (P=0.0032). (D) Patients with negative nuclear NF-κB expression, PSA<10 ng ml−1 and Gleason⩽6 presented had a better prognosis compared to patients with negative nuclear NF-κB expression and one (PSA⩾10 ng ml−1 or gleason⩾7) or both (PSA⩾10 ng ml−1 and gleason⩾7) adverse independent prognostic factors (P=0.046).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2361509&req=5

fig3: Upper panels, Kaplan–Meier survival curves for cytoplasmic and nuclear NF-κB expression in prostate adenocarcinomas. (A) No association between NF-κB cytoplasmic expression and biochemical disease recurrence was detected (P=0.74). (B) Nuclear expression of NF-κB was associated to the chance of biochemical disease-free survival. Patients with nuclear NF-κB had a higher risk of biochemical disease recurrence compared with those whose primary tumours did not have nuclear NF-κB (P=0.0009). Lower panels, Kaplan–Meier survival curves for NF-κB nuclear expression combined with presurgical serum prostate specific antigen (PSA) levels and Gleason score. (C) Patients with positive nuclear NF-κB expression and both (PSA⩾10 ng ml−1 and gleason ⩾7) adverse prognostic factors had a greater chance of biochemical disease recurrence than those who presented one (PSA⩾10 ng ml−1 or gleason ⩾7) or no (PSA⩽10 ng ml−1 and gleason⩽6) adverse independent prognostic factors (P=0.0032). (D) Patients with negative nuclear NF-κB expression, PSA<10 ng ml−1 and Gleason⩽6 presented had a better prognosis compared to patients with negative nuclear NF-κB expression and one (PSA⩾10 ng ml−1 or gleason⩾7) or both (PSA⩾10 ng ml−1 and gleason⩾7) adverse independent prognostic factors (P=0.046).
Mentions: The relationship between NF-κB expression and the risk of biochemical relapse was assessed using Kaplan–Meier disease outcome analysis. Using a bimodal approach, the presence or absence of NF-κB cytoplasmic staining was not associated with the risk of biochemical relapse of the disease (Figure 3A; log-rank test, P=0.74). Using a semiquantitative scoring assessment approach (0, +, ++, +++), cytoplasmic NF-κB expression was similarly not significantly associated with the risk of biochemical relapse (data not shown).

Bottom Line: By univariate analysis, nuclear localisation of NF-kappaB was associated with biochemical relapse (P=0.0009; log-rank test) while cytoplasmic expression did not.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Oncology, Hospital Clinic & Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

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.

Show MeSH
Related in: MedlinePlus