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Expression of Nuclear Factor-B and IB Proteins in Prostatic Adenocarcinomas

Correlation of Nuclear Factor-B Immunoreactivity with Disease Recurrence

Departments of ¹ Pathology and Laboratory Medicine and ² Surgery, Albany Medical College, Albany, New York; ³ Georgetown University Hospital, Washington, DC; ⁴ Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts

Purpose: The nuclear transcription factor nuclear factor-B (NFB) and its inhibitor, IB, regulate the transcription of various genes involved in cell proliferation, adhesion, and survival. The NFB transcription factor complex plays a role in cancer development and progression through its influence on apoptosis. More recently, NFB 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 NFB immunoreactivity in prostate adenocarcinomas (PACs).

Experimental Design: Using prostatectomy specimens, we performed immunohistochemical staining for NFB and IB (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 NFB, and 63% showed decreased IB expression. Cytoplasmic NFB 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 NFB-positive and -negative subgroups, NFB overexpression correlated with preoperative serum prostate-specific antigen (P = 0.04) and DNA index (P = 0.05). Fifteen percent of PACs expressed nuclear NFB, which correlated with high tumor grade (P = 0.001) and advanced stage (P = 0.05). Decreased IB expression correlated with high tumor grade (P = 0.015). On multivariate analysis, tumor stage (P = 0.043) and NFB overexpression (P = 0.006) were independent predictors of biochemical recurrence.

Conclusion: These results support a role for NFB 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 NFB blockade in decreasing the rate of disease relapse.

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