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

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

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28 Citations (Scopus)

Abstract

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-IκBβ (P = 0.002 and P = 0.05, respectively), and IκBβ mRNAexpression (P = 0.032). In contrast, phospho-p65 expression was paralleled by the expression of nuclear (P = 0.027) and cytoplasmic phospho-IκBβ (P = 0.01). Total p65 expression was an adverse prognostic factor for overall survival (P = 0.018). In contrast, total IκBβ and phosphorylated nuclear and cytoplasmic IκBβ expression were favourable prognostic markers (P = 0.001, P = 0.031, P = 0.001, respectively). Cytoplasmic phospho-IκBβ 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 IκBβ 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.

Original languageEnglish
Pages (from-to)727-739
Number of pages13
JournalHistopathology
Volume56
Issue number6
DOIs
Publication statusPublished - May 1 2010

Keywords

  • Classical NF-κB pathway
  • Ovarian cancer
  • Prognosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

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  • Cite this

    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). Expression of classical NF-κB pathway effectors in human ovarian carcinoma. Histopathology, 56(6), 727-739. https://doi.org/10.1111/j.1365-2559.2010.03544.x