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Immunohistochemical assessment of Survivin and Bcl3 expression as potential biomarkers for NF-κB activation in the Barrett metaplasia-dysplasia-adenocarcinoma sequence

Puccio, I; Khan, S; Butt, A; Graham, D; Sehgal, V; Patel, D; Novelli, M; ... Hamoudi, RA; + view all (2018) Immunohistochemical assessment of Survivin and Bcl3 expression as potential biomarkers for NF-κB activation in the Barrett metaplasia-dysplasia-adenocarcinoma sequence. International Journal of Experimental Pathology , 99 (1) pp. 10-14. 10.1111/iep.12260. Green open access

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Abstract

Non-dysplastic Barrett's oesophagus (NDBE) occurs as a consequence of an inflammatory response triggered through prolonged gastro-oesophageal reflux and it may precede the development of oesophageal adenocarcinoma. NF-κB activation as a result of the inflammatory response has been shown in NDBE, but the possible mechanism involved in the process is unknown. The aim of this study was to assess, using immunohistochemistry, Survivin and Bcl3 expression as potential biomarkers for NF-κB activation along the oesophageal metaplasia-dysplasia-adenocarcinoma sequence. Survivin is an NF-κB-inducible anti-apoptotic protein, and Bcl3 is a negative regulator of NF-κB. There was progressive upregulation of Survivin expression along the oesophageal metaplasia-dysplasia-adenocarcinoma sequence. Bcl3 expression was upregulated in non-dysplastic Barrett's oesophagus, low-grade, high-grade dysplasia and oesophageal adenocarcinoma when compared to squamous group. The study shows the differential expression of Bcl3 between the squamous and Barrett's stage, suggesting that Bcl3 could be a surrogate marker for early event involving constitutive NF-κB activation. In addition, the study suggests that NF-κB activation may infer resistance to apoptosis through the expression of anti-apoptotic genes such as Survivin, which showed progressive increase in expression throughout the oesophageal metaplasia-dysplasia-adenocarcinoma sequence. This ability to avoid apoptosis may underlie the persistence and malignant predisposition of Barrett's metaplasia.

Type: Article
Title: Immunohistochemical assessment of Survivin and Bcl3 expression as potential biomarkers for NF-κB activation in the Barrett metaplasia-dysplasia-adenocarcinoma sequence
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1111/iep.12260
Publisher version: http://dx.doi.org/10.1111/iep.12260
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Barrett's oesophagus, Bcl3, Survivin, immunohistochemistry, inflammatory response, nuclear factor kappa B
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Pathology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Surgery and Interventional Sci > Department of Targeted Intervention
URI: https://discovery.ucl.ac.uk/id/eprint/10044635
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