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Expression of nuclear factor-kappa B and I kappa B alpha proteins in prostatic adenocarcinomas: correlation of nuclear factor-kappa B immunoreactivity with disease recurrence.

AbstractPURPOSE:
The nuclear transcription factor nuclear factor-kappa B (NF kappa B) and its inhibitor, I kappa B, regulate the transcription of various genes involved in cell proliferation, adhesion, and survival. The NF kappa B transcription factor complex plays a role in cancer development and progression through its influence on apoptosis. More recently, NF kappa B has been shown to be activated in human and androgen-independent prostate cancer cells. To our knowledge, this is the first study demonstrating the prognostic significance of NF kappa B immunoreactivity in prostate adenocarcinomas (PACs).
EXPERIMENTAL DESIGN:
Using prostatectomy specimens, we performed immunohistochemical staining for NF kappa B and I kappa B alpha (Santa Cruz Biotechnology) on formalin-fixed, paraffin-embedded sections obtained from 136 patients with PAC. Cytoplasmic and nuclear immunoreactivity was scored for intensity and distribution, and results were correlated with preoperative serum prostate-specific antigen, tumor grade, stage, DNA ploidy (Feulgen spectroscopy), and biochemical disease recurrence.
RESULTS:
Forty-nine percent of PACs overexpressed cytoplasmic NF kappa B, and 63% showed decreased I kappa B expression. Cytoplasmic NF kappa B overexpression correlated with advanced tumor stage (P = 0.048), aneuploidy (P = 0.022), and biochemical disease recurrence (P = 0.001). When we compared the means for the NF kappa B-positive and -negative subgroups, NF kappa B overexpression correlated with preoperative serum prostate-specific antigen (P = 0.04) and DNA index (P = 0.05). Fifteen percent of PACs expressed nuclear NF kappa B, which correlated with high tumor grade (P = 0.001) and advanced stage (P = 0.05). Decreased I kappa B alpha expression correlated with high tumor grade (P = 0.015). On multivariate analysis, tumor stage (P = 0.043) and NF kappa B overexpression (P = 0.006) were independent predictors of biochemical recurrence.
CONCLUSION:
These results support a role for NF kappa B pathway proteins in the tumorigenesis of PACs. The findings are also consistent with reported experimental studies suggesting a new strategy of combined chemotherapy and specific NF kappa B blockade in decreasing the rate of disease relapse.
AuthorsJeffrey S Ross, Bhaskar V S Kallakury, Christine E Sheehan, Hugh A G Fisher, Ronald P Kaufman Jr, Prabhjot Kaur, Karen Gray, Bradley Stringer
JournalClinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 10 Issue 7 Pg. 2466-72 (Apr 01 2004) ISSN: 1078-0432 [Print] United States
PMID15073126 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • I-kappa B Proteins
  • NF-kappa B
  • NFKBIA protein, human
  • NF-KappaB Inhibitor alpha
  • DNA
Topics
  • Adenocarcinoma (metabolism, pathology)
  • Aged
  • Aged, 80 and over
  • Apoptosis
  • Cell Adhesion
  • Cell Division
  • Cell Nucleus (metabolism)
  • Cell Survival
  • Cytoplasm (metabolism)
  • DNA (chemistry)
  • Humans
  • I-kappa B Proteins (biosynthesis)
  • Immunohistochemistry
  • Male
  • Middle Aged
  • NF-KappaB Inhibitor alpha
  • NF-kappa B (biosynthesis, metabolism)
  • Prognosis
  • Prostatic Neoplasms (metabolism, pathology)
  • Recurrence
  • Time Factors

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