NF-κB nuclear localization and its prognostic significance in prostate cancer

被引:109
作者
Lessard, L
Mes-Masson, AM
Lamarre, L
Wall, L
Lattouf, JB
Saad, F
机构
[1] Hop Notre Dame de Bon Secours, CHUM, Ctr Rech, Montreal, PQ H2L 4K8, Canada
[2] Hop Notre Dame de Bon Secours, CHUM, Dept Urol, Montreal, PQ H2L 4K8, Canada
[3] Hop Notre Dame de Bon Secours, CHUM, Dept Pathol, Montreal, PQ H2L 4K8, Canada
[4] Univ Montreal, Inst Canc Montreal, Montreal, PQ H2L 4M1, Canada
关键词
prostatic neoplasm; NF-kappa B; prognostic marker; immunohistochemistry; Gleason grade;
D O I
10.1046/j.1464-410X.2003.04104.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
OBJECTIVE To detect the subcellular localization of NF-kappaB (p65) in human prostate cancer tissues of different histological grades, and to test whether NF-kappaB localization alone, or combined with the histological grade, can be used to predict patient outcome. PATIENTS AND METHODS Prostate cancer tissues were obtained from radical prostatectomy specimens; the histological grade was determined using the Gleason grading system. Clinical outcomes were defined as good (5-year disease-free survival with undetectable levels of prostate specific antigen) or poor (progression to bone metastases). The subcellular localization of NF-kappaB was visualized by immunohistochemistry using an anti-p65 antibody. RESULTS The NF-kappaB subcellular localization was initially assessed in 45 specimens; in these samples a nuclear localization of NF-kappaB was specific to cancer tissues, but did not correlate with the Gleason score (P = 0.089). NF-kappaB was then assessed as a prognostic marker to complement Gleason score in predicting cancer progression. Tumour tissues from 30 men with a known clinical outcome were included; 10 of 17 patients who had a poor outcome were positive for NF-kappaB nuclear staining, whereas only two of 13 with a good outcome were positive (P = 0.026). When NF-kappaB subcellular localization and Gleason score were combined, two risk categories of progression were defined. Eleven of 13 specimens from those with a good outcome were in the low-risk category (Gleason 2-4 or Gleason 5-7 with negative nuclear NF-kappaB) and 12 of 17 in the poor outcome group were in the high-risk category (Gleason 8-10 or Gleason 5-7 with positive nuclear NF-kappaB; P = 0.004). CONCLUSION NF-kappaB is detectable in the nucleus in prostate cancer tissues and positivity can be used to help predict patient outcome. Multivariate analyses using other clinical and molecular variables are underway, and will validate the usefulness of NF-kappaB as a prognostic factor.
引用
收藏
页码:417 / 420
页数:4
相关论文
共 29 条
[1]   Molecular genetics of prostate cancer [J].
Abate-Shen, C ;
Shen, MM .
GENES & DEVELOPMENT, 2000, 14 (19) :2410-2434
[2]   Control of oncogenesis and cancer therapy resistance by the transcription factor NF-κB [J].
Baldwin, AS .
JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (03) :241-246
[3]   Control of apoptosis by Rel/NF-κB transcription factors [J].
Barkett, M ;
Gilmore, TD .
ONCOGENE, 1999, 18 (49) :6910-6924
[4]   GLEASON GRADING OF PROSTATIC NEEDLE BIOPSIES - CORRELATION WITH GRADE IN 316 MATCHED PROSTATECTOMIES [J].
BOSTWICK, DG .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 1994, 18 (08) :796-803
[5]   NF-κB activates prostate-specific antigen expression and is upregulated in androgen-independent prostate cancer [J].
Chen, CD ;
Sawyers, CL .
MOLECULAR AND CELLULAR BIOLOGY, 2002, 22 (08) :2862-2870
[6]  
Chung TDK, 1999, PROSTATE, V38, P199
[7]  
Gasparian AV, 2002, J CELL SCI, V115, P141
[8]   Missing pieces in the NF-κB puzzle [J].
Ghosh, S ;
Karin, M .
CELL, 2002, 109 :S81-S96
[9]   The Rel/NF-κB signal transduction pathway:: introduction [J].
Gilmore, TD .
ONCOGENE, 1999, 18 (49) :6842-6844
[10]   Interleukin-6 is an autocrine growth factor in human prostate cancer [J].
Giri, D ;
Ozen, M ;
Ittmann, M .
AMERICAN JOURNAL OF PATHOLOGY, 2001, 159 (06) :2159-2165