Inverse expression of estrogen receptor-beta and nuclear factor-kappaB in urinary bladder carcinogenesis.
OBJECTIVE
To investigate the expression of nuclear factor-kappaB (NF-kappaB) 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-kappaB, 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-kappaB 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-kappaB was shown. No correlation between NF-kappaB, 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-kappaB and ER-beta transcription factor during bladder carcinogenesis. Selective ER-beta agonists and agents, inhibitors of NF-kappaB, might represent a possible new treatment strategy for bladder urothelial tumors.
Kontos
Stylianos
S
Departments of Pathology, University of Patras, Rion, Greece. kontostylianos@gmail.com
Kominea
Athina
A
Melachrinou
Maria
M
Balampani
Eleni
E
Sotiropoulou-Bonikou
Georgia
G
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000737:chemistry / Q000209:etiology / Q000378:metabolism*; D047629:Estrogen Receptor beta / Q000032:analysis / Q000096:biosynthesis* / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000032:analysis / Q000096:biosynthesis* / Q000502:physiology; D001749:Urinary Bladder Neoplasms / Q000737:chemistry / Q000209:etiology / Q000378:metabolism*; D055815:Young Adult
D047629:Estrogen Receptor beta; D016328:NF-kappa B