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

OBJECTIVE

to examine the hypothesis that nuclear factor-κB (NF-κB), 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-κB (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-κB, and nuclear immunoreactivity for NF-κB 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-κB expression. On multivariate analysis, nuclear NF-κB 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-κB expression in the tumorigenesis of UUT-UC. Nuclear NF-κB may serve as a useful independent molecular marker to predict outcome and may represent a promising therapeutic target for patients with UUT-UC.