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Expression of classical NF‐κB pathway effectors in human ovarian carcinoma

2010; Wiley; Volume: 56; Issue: 6 Linguagem: Inglês

10.1111/j.1365-2559.2010.03544.x

1365-2559

Silvia Darb‐Esfahani, Bruno V. Sinn, Wilko Weichert, Jan Budczies, Annika Lehmann, Aurelia Noske, Ann‐Christin Buckendahl, Berit Müller, Jalid Sehouli, Dominique Koensgen, Balázs Győrffy, Manfred Dietel, Carsten Denkert,

Cell death mechanisms and regulation

Darb‐Esfahani S, Sinn B V, Weichert W, Budczies J, Lehmann A, Noske A, Buckendahl A‐C, Müller B M, Sehouli J, Koensgen D, Györffy B, Dietel M & Denkert C (2010) Histopathology 56. 727–739 Expression of classical NF‐κB pathway effectors in human ovarian carcinoma Aims: Functional studies have demonstrated that nuclear factor (NF)‐κB promotes tumour progression in ovarian cancer cells. However, surprisingly little is known of the expression of effectors of the NF‐κB pathway in human ovarian cancer in vivo . Methods and results: Immunohistochemistry and in situ hybridization revealed that in a cohort of 85 primary ovarian carcinomas, total p65 expression was inversely correlated to nuclear and cytoplasmic phospho‐IκBα ( P = 0.002 and P = 0.05, respectively), and IκBα mRNA expression ( P = 0.032). In contrast, phospho‐p65 expression was paralleled by the expression of nuclear ( P = 0.027) and cytoplasmic phospho‐IκBα ( P = 0.01). Total p65 expression was an adverse prognostic factor for overall survival ( P = 0.018). In contrast, total IκBα and phosphorylated nuclear and cytoplasmic IκBα expression were favourable prognostic markers ( P = 0.001, P = 0.031, P = 0.001, respectively). Cytoplasmic phospho‐IκBα expression remained a significant prognostic factor on multivariate analysis ( P = 0.010). In cultured, stimulated OVCAR‐3 ovarian cancer cells the cytoplasmic retranslocation of p65 was delayed by inhibition of the nuclear membrane transporter chromosomal region maintenance/exportin1 protein (CRM1). A positive association of p65 and CRM1 expression was demonstrated in ovarian cancer tissue ( P < 0.0001). Conclusions: Total and phosphorylated IκBα protein expression might serve as markers for NF‐κB activation in human ovarian carcinoma. Cytoplasmic localization of p65 may be related to deregulated nucleocytoplasmic transport in carcinomas overexpressing CRM1.