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, B. Györffy, Manfred Dietel, Carsten Denkert

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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 2010

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Ovarian Neoplasms
Carcinoma
Membrane Transport Proteins
Cell Nucleus Active Transport
Nuclear Envelope
In Situ Hybridization
Multivariate Analysis
Immunohistochemistry
Maintenance
Survival
Neoplasms
Proteins

Keywords

  • Classical NF-κB pathway
  • Ovarian cancer
  • Prognosis

ASJC Scopus subject areas

  • Histology
  • Pathology and Forensic Medicine
  • Medicine(all)

Cite this

Darb-Esfahani, S., Sinn, B. V., Weichert, W., Budczies, J., Lehmann, A., Noske, A., ... 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

Expression of classical NF-κB pathway effectors in human ovarian carcinoma. / Darb-Esfahani, Silvia; Sinn, Bruno V.; Weichert, Wilko; Budczies, Jan; Lehmann, Annika; Noske, Aurelia; Buckendahl, Ann Christin; Müller, Berit Maria; Sehouli, Jalid; Koensgen, Dominique; Györffy, B.; Dietel, Manfred; Denkert, Carsten.

In: Histopathology, Vol. 56, No. 6, 05.2010, p. 727-739.

Research output: Contribution to journalArticle

Darb-Esfahani, S, Sinn, BV, Weichert, W, Budczies, J, Lehmann, A, Noske, A, Buckendahl, AC, Müller, BM, Sehouli, J, Koensgen, D, Györffy, B, Dietel, M & Denkert, C 2010, 'Expression of classical NF-κB pathway effectors in human ovarian carcinoma', Histopathology, vol. 56, no. 6, pp. 727-739. https://doi.org/10.1111/j.1365-2559.2010.03544.x
Darb-Esfahani S, Sinn BV, Weichert W, Budczies J, Lehmann A, Noske A et al. Expression of classical NF-κB pathway effectors in human ovarian carcinoma. Histopathology. 2010 May;56(6):727-739. https://doi.org/10.1111/j.1365-2559.2010.03544.x
Darb-Esfahani, Silvia ; Sinn, Bruno V. ; Weichert, Wilko ; Budczies, Jan ; Lehmann, Annika ; Noske, Aurelia ; Buckendahl, Ann Christin ; Müller, Berit Maria ; Sehouli, Jalid ; Koensgen, Dominique ; Györffy, B. ; Dietel, Manfred ; Denkert, Carsten. / Expression of classical NF-κB pathway effectors in human ovarian carcinoma. In: Histopathology. 2010 ; Vol. 56, No. 6. pp. 727-739.
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AU - Lehmann, Annika

AU - Noske, Aurelia

AU - Buckendahl, Ann Christin

AU - Müller, Berit Maria

AU - Sehouli, Jalid

AU - Koensgen, Dominique

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