High expression of RelA/p65 is associated with activation of nuclear factor-kappaB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis

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Item Type:	Article
Title:	High expression of RelA/p65 is associated with activation of nuclear factor-kappaB-dependent signaling in pancreatic cancer and marks a patient population with poor prognosis
Creators Name:	Weichert, W., Boehm, M., Gekeler, V., Bahra, M., Langrehr, J., Neuhaus, P., Denkert, C., Imre, G., Weller, C., Hofmann, H.P., Niesporek, S., Jacob, J., Dietel, M., Scheidereit, C. and Kristiansen, G.
Abstract:	Activation of nuclear factor-kappaB (NF-kappaB) signaling was observed in pancreatic adenocarcinoma cell lines and tumours. However, information on the expression of RelA/p65, the major transcription activating NF-kappaB subunit, in these carcinomas and possible correlations thereof with NF-kappaB activation and patient survival is not available. To provide this missing translational link, we analysed expression of RelA/p65 in 82 pancreatic adenocarcinomas by immunohistochemistry. Moreover, we measured activation of the NF-kappaB pathway in 11 tumours by quantitative PCR for NF-kappaB target genes. We observed strong cytoplasmic or nuclear expression of RelA/p65 in 42 and 37 carcinomas, respectively. High cytoplasmic and nuclear expression of RelA/p65 had negative prognostic impact with 2-year survival rates for patients without cytoplasmic or nuclear RelA/p65 positivity of 41 and 40% and rates for patients with strong cytoplasmic or nuclear RelA/p65 expression of 22 and 20%, respectively. High RelA/p65 expression was correlated to increased expression of NF-kappaB target genes. The observation that high expression of RelA/p65 is correlated to an activation of the NF-kappaB pathway and indicates poor patient survival identifies a patient subgroup that might particularly benefit from NF-kappaB-inhibiting agents in the treatment of pancreatic cancer. Based on our findings, this subgroup could be identified by applying simple immunohistochemical techniques.
Keywords:	NF-kappaB, Pancreatic carcinoma, RelA, Prognosis, Survival, Immunohistochemistry
Source:	British Journal of Cancer
ISSN:	0007-0920
Publisher:	Nature Publishing Group
Volume:	97
Page Range:	523-530
Date:	14 August 2007
Official Publication:	https://doi.org/10.1038/sj.bjc.6603878
PubMed:	View item in PubMed

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