Clinical significance of nuclear factor (NF)-κB 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.

Glycogen Synthase Kinase-3β: A Prognostic Marker and a Potential Therapeutic Target in Human Bladder Cancer

“…NF-κB is known to play a role in human cancer progression and chemoresistance (32,33), in part through positive regulation of its target genes XIAP (34) and Bcl-2 (35). Levidou et al showed that the nuclear expression of NF-κB was correlated with the histologic grade and stage in bladder cancer (33).…”

“…NF-κB is known to play a role in human cancer progression and chemoresistance (32,33), in part through positive regulation of its target genes XIAP (34) and Bcl-2 (35). Levidou et al showed that the nuclear expression of NF-κB was correlated with the histologic grade and stage in bladder cancer (33). Our previous studies revealed that high expression of Bcl-2 and/or XIAP defines urothelial carcinomas with higher metastatic potential and poor prognosis (25,36).…”

D-type cyclins in superficial and muscle-invasive bladder urothelial carcinoma: correlation with clinicopathological data and prognostic significance

“…Overexpression of D-type cyclins has been reported in various solid tumours (Büschges et al 1999;Lopez-Beltran et al 2004a, b;Jiang et al 1993;Takano et al 1999;Levidou et al 2007). However, contemporary literature suggests that the relationship between D-type cyclins and oncogenesis may not be as simple as initially thought, since under diVerent circumstances they may act either as promoters of proliferation or as inducers of diVerentiation (Pagano et al 1994;Gao et al 2004;Gillett et al 1996;Peng et al 1998;Levidou et al 2008).…”

Prognostic Role of KiSS-1 and Possibility of Therapeutic Modality of Metastin, the Final Peptide of the KiSS-1 Gene, in Urothelial Carcinoma

“…tumor invasiveness and aggressive behavior in bladder cancer patients (33). Another report showed that highly metastatic bladder cancer cells constitutively express high levels of NF-kB, whereas less aggressive bladder cancer cells express lower levels of NF-kB activity (34).…”