Abstract | PURPOSE: 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.
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Authors | Jeffrey S Ross, Bhaskar V S Kallakury, Christine E Sheehan, Hugh A G Fisher, Ronald P Kaufman Jr, Prabhjot Kaur, Karen Gray, Bradley Stringer |
Journal | Clinical 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 |
PMID | 15073126
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- I-kappa B Proteins
- NF-kappa B
- NFKBIA protein, human
- NF-KappaB Inhibitor alpha
- DNA
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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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