Inverse expression of estrogen receptor-β and nuclear factor-κB in urinary bladder carcinogenesis

Objectives: To investigate the expression of nuclear factor-kappa B (NF-kappa B) and estrogen receptor-beta (ER-beta) signalling pathways in bladder urothelial carcinoma according to clinicopathological features, in order to elucidate their role during carcinogenesis. Methods: Immunohistochemical methodology was carried out on formalin-fixed, paraffin-embedded sections from urinary bladder carcinomas of 140 patients ( 94 males and 46 females) who underwent transurethral resection of bladder neoplasms. Correlations between ER-beta and NF-kappa B, and tumor grade and T-stage were evaluated, along with demographic data, sex and age. Results: A significant decrease in ER-beta expression in the nucleus of bladder cells during loss of cell differentiation (r(s) = -0.61, P-value < 0.001, test of trend P-value = 0.003) and in muscle invasive carcinomas (T2-T4; test of trend P-value < 0.001) was found. p65 Subunit of NF-kappa B was expressed in the nucleus and in the cytoplasm of bladder epithelial cells. A strong positive association between tumor grade and nuclear expression of NF-kappa B was shown. No correlation between NF-kappa B, nuclear or cytoplasmic staining, with T-stage was observed. An inverse correlation between ER-beta and nuclear p65 immunoreactivity was observed (r(s) = -0.45, P-value < 0.001). There was no correlation with demographic data. Conclusions: Our immunohistochemical study suggests the possible inverse regulation of NF-kappa B and ER-beta transcription factor during bladder carcinogenesis. Selective ER-beta agonists and agents, inhibitors of NF-kappa B, might represent a possible new treatment strategy for bladder urothelial tumors.