title: Clinical significance of nuclear factor (NF)-kappaB levels in urothelial carcinoma of the urinary bladder.
abstract: Nuclear factor (NF)-kappaB has been reported to be constitutively activated in various human neoplasms. However, its clinical significance in bladder urothelial carcinoma (UC) remains an unresolved issue. We conducted this study trying to elucidate the role of NFkappaB in bladder UC and its potential prognostic significance, by quantifying immunohistochemically the levels of p65/RelA expression in paraffin-embedded tissue from 116 patients. Some of the cases had previously been stained for cellular FLICE-like inhibitory protein (c-FLIP) and bcl-2. Seventy-four cases displayed concurrent cytoplasmic and nuclear immunoreactivity, whereas 18 only nuclear immunoexpression and 21 only cytoplasmic immunoexpression, and the remaining three cases were negative for p65/RelA. Nuclear p65/RelA expression was positively associated with tumour grade and T-category (p=0.0001 in both cases). In addition, cytoplasmic p65/RelA expression was lower in advanced T-category (p=0.0030). Moreover, p65/RelA nuclear expression was positively correlated with c-FLIP (p=0.0109) and bcl-2 (p=0.0452). p65/RelA nuclear expression adversely affected survival in both univariate and multivariate analysis in superficial (Ta-T1; p=0.0010 and p=0.0008) as well as in muscle-invasive carcinomas (T2-T4; p=0.0004 and p=0.0003). Our results demonstrate that NF-kappaB nuclear expression is correlated with histologic grade and T category in bladder UC. Moreover, NF-kappaB nuclear expression emerges as an independent prognosticator of adverse significance, conveying information beyond that obtained by standard clinicopathological prognosticators.
authors.affiliation: Department of Pathology, National and Kapodistrian University of Athens, 75 Mikras Asias Street, Athens 11527, Greece. glevidou@yahoo.gr
authors.forename: Georgia
authors.initials: G
authors.lastname: Levidou
authors.forename: Angelica A
authors.initials: AA
authors.lastname: Saetta
authors.forename: Penelope
authors.initials: P
authors.lastname: Korkolopoulou
authors.forename: Polyanthi
authors.initials: P
authors.lastname: Papanastasiou
authors.forename: Katerina
authors.initials: K
authors.lastname: Gioti
authors.forename: Petros
authors.initials: P
authors.lastname: Pavlopoulos
authors.forename: Kalliopi
authors.initials: K
authors.lastname: Diamantopoulou
authors.forename: Eupthemia
authors.initials: E
authors.lastname: Thomas-Tsagli
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Xiromeritis
authors.forename: Efstratios
authors.initials: E
authors.lastname: Patsouris
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002467:Cell Nucleus / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016328:NF-kappa B / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*; D019459:Urothelium / Q000737:chemistry / Q000473:pathology*
chemical_list: D016328:NF-kappa B; D051996:Transcription Factor RelA