Nuclear factor-κB activation predicts an unfavourable outcome in human upper urinary tract urothelial carcinoma

OBJECTIVE To examine the hypothesis that nuclear factor-kappa B (NF-kappa B), a transcription factor involved in anti-apoptosis, invasion, and angiogenesis, plays a role in the carcinogenesis of upper urinary tract urothelial carcinoma (UUT-UC) and has prognostic value for survival. PATIENTS AND METHODS In all, 90 patients with UUT-UC [mean (range) age, 64.5 (24-84) years] who underwent surgery at our institution from January 1991 to December 2005 were included. Clinicopathological data were collected retrospectively. We performed immunohistochemical staining for NF-kappa B (p65) on paraffin-embedded sections of the tumour and corresponding normal tissues. The association between survival and potential prognostic factors was examined. RESULTS The median follow-up was 40 months. In all, 55 patients (61.1%) with UUT-UC overexpressed cytoplasmic NF-kappa B, and nuclear immunoreactivity for NF-kappa B was detected in 24 patients (26.7%). On univariate analysis, significant prognostic factors for survival were tumour location, stage, grade, lymph node involvement, and nuclear NF-kappa B expression. On multivariate analysis, nuclear NF-kappa B positivity was an independent predictor for disease-specific survival [Cox regression hazard ratio (HR) 2.87; P = 0.025] and overall survival (HR 2.24; P = 0.037). CONCLUSION These results imply a role for nuclear NF-kappa B expression in the tumorigenesis of UUT-UC. Nuclear NF-kappa B may serve as a useful independent molecular marker to predict outcome and may represent a promising therapeutic target for patients with UUT-UC.