Expression of nuclear factor kappaB in human gastric carcinoma: relationship with I kappaB a and prognostic significance.

Nuclear factor (NF)-kappaB is a transcription factor constitutively activated in various neoplasms, including gastric carcinoma. However, its clinical significance in the latter remains an unresolved issue, as published information is limited and controversial. Furthermore, no data is available about the interaction of NF kappaB with its inhibitory protein I kappaB a in gastric carcinoma cases. In this study, the expression of NF kappaB 1/p50 and p I kappaB a protein was evaluated immunohistochemically in paraffin-embedded tissues from 93 patients. The effect of NF kappaB 1/p50 and p I kappaB a on clinical outcome was assessed. Positive immunostaining was detected for nuclear NF kappaB 1/p50, cytoplasmic NF kappa B1/p50 and p I kappaB a in 91, 68 and 85.7% of cases, respectively. A positive correlation emerged between nuclear NF kappa B 1/p50 and p I kappaB a (p < 0.0001) and a negative one between cytoplasmic NF kappaB 1/p50 and p I kappaB a (p = 0.0033). Nuclear NF kappaB 1/p50 was associated with stage (p = 0.0388), the depth of invasion (p = 0.0382), World Health Organization (WHO; p = 0.0326) and Lauren's histological classification (p = 0.0046). NF kappaB 1/p50 nuclear expression adversely affected survival in both univariate and multivariate analysis (p < 0.0001 and p = 0.02, respectively). Our results suggest that NF kappaB 1/p50 nuclear expression and therefore activation is regulated by its interaction with I kappaB a and that the former may serve as a useful independent molecular marker for stratifying patients with gastric carcinoma in terms of prognosis.