Oesophagus / Esofago (C15.9) - Apoptotic frequencies are inversely re­lated to levels of cell survival proteins in neoplastic development in patients with Barrett’s oesophagus

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Zakaria Eltahir
Gareth James Scott Jenkins
John Neville Baxter
Lynda Hopkins
Anthony Paul Griffiths

Keywords

Barrett’s oesophagus, apoptosis, BCL-XL, NF-kB

Abstract

Purpose: We aimed here to assess the apoptotic cell frequency in Barrett’s oesophagus tissue and the histological series leading to adenocarcinoma. In parallel, we also aimed to quantify the expression of several anti-apoptotic proteins. The purpose was to assess the role of these anti-apoptotic proteins in apoptosis resistance across this well defined neoplastic series. Methods: Apoptotic bodies were manually counted in 74 biopsy tissue sections after robust training (and the use of CD45 and caspase 3 as internal controls). Immunohistochemistry was used to measure the expression of BCL-XL, XIAP and BCL-2 in a subset of the same sections. Results: Apoptotic frequency dropped from 0.2% in the Barrett’s oesophagus and low grade dysplasia groups to <0.1% in the high grade dysplasia and adenocarcinoma groups. In parallel a marked increase in BCL-XL expression as the tissue progressed towards adenocarcinoma was observed. Moreover a non-significant increase in XIAP expression was detected. BCL-2 expression was low and did not change during the histological advancement. Conclusions: Anti-apoptotic protein expression increased across the histological series to cancer in Barrett’s oesophagus. This occurred in an inverse manner to the level of apoptotic cells. Apoptotic resistance may drive neoplastic development in the oesophagus and BCL-XL may be prime target for therapy.
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