Increased expression of the 5-lipoxygenase pathway and its cellular localization in Barrett's adenocarcinoma
Increased expression of the 5-lipoxygenase pathway and its cellular localization in Barrett's adenocarcinoma
Aims: Up‐regulation of the 5‐lipoxygenase (5‐LOX) leukotriene pathway is evident in numerous tumour types, and has been linked to the promotion of cancer cell growth. The aim of this study was to evaluate the immunohistochemical expression of 5‐LOX pathway proteins in oesophageal adenocarcinoma and its premalignant lesion, Barrett’s metaplasia.
Methods and results: Tissue samples were collected at endoscopy from 16 patients with Barrett’s metaplasia and from seven with oesophageal adenocarcinoma; five proximal squamous oesophagus samples were used as controls. Immunohistochemical analyses were performed on stromal and epithelial areas with optimized concentrations of primary antibodies for 5‐LOX, 5‐LOX‐activating protein (FLAP), and the distal enzymes leukotriene (LT) A4 hydrolase (LTA4H) and LTC4 synthase (LTC4S). the diagnosis was histologically confirmed from adjacent sections by a gastrointestinal pathologist. Striking increases in the stromal immunoexpression of 5‐LOX (P = 0.041), FLAP (P = 0.038), LTA4H (P = 0.0008) and LTC4S (P = 0.036) were seen in adenocarcinoma tissue. Stromal FLAP and LTA4H immunostaining correlated with elevated neutrophil counts (P < 0.001). LTC4S was also notably overexpressed within epithelial cells in both Barrett’s metaplasia (P < 0.001) and adenocarcinoma (P < 0.01) tissue.
Conclusions: Key biosynthetic enzymes of the LTB4 and LTC4 biosynthetic pathways are incrementally expressed across the spectrum of squamous, Barrett’s metaplasia and oesophageal adenocarcinoma tissues, suggesting, for the first time, a role for both LT subfamilies in disease progression.
509-517
Boger, Philip C.
607d1fe1-1d27-4461-a268-93d5dfa649a3
Shutt, James D.
45eb6f7c-fe4e-44e1-af6f-c091348b4b64
Neale, James R.
21737dff-f26a-4085-942e-e32ef77fd701
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Bateman, Adrian C.
28ae82e3-b93a-429a-81f5-04e8f1ff4cc7
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Patel, Praful
c92dd012-6d09-43b2-9fac-aaadcb42ea27
Sampson, Anthony P.
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60
September 2012
Boger, Philip C.
607d1fe1-1d27-4461-a268-93d5dfa649a3
Shutt, James D.
45eb6f7c-fe4e-44e1-af6f-c091348b4b64
Neale, James R.
21737dff-f26a-4085-942e-e32ef77fd701
Wilson, Susan J.
21c6875d-6870-441b-ae7a-603562a646b8
Bateman, Adrian C.
28ae82e3-b93a-429a-81f5-04e8f1ff4cc7
Holloway, John W.
4bbd77e6-c095-445d-a36b-a50a72f6fe1a
Patel, Praful
c92dd012-6d09-43b2-9fac-aaadcb42ea27
Sampson, Anthony P.
4ca76f6f-ff35-425d-a7e7-c2bd2ea2df60
Boger, Philip C., Shutt, James D., Neale, James R., Wilson, Susan J., Bateman, Adrian C., Holloway, John W., Patel, Praful and Sampson, Anthony P.
(2012)
Increased expression of the 5-lipoxygenase pathway and its cellular localization in Barrett's adenocarcinoma.
Histopathology, 61 (3), .
(doi:10.1111/j.1365-2559.2012.04258.x).
Abstract
Aims: Up‐regulation of the 5‐lipoxygenase (5‐LOX) leukotriene pathway is evident in numerous tumour types, and has been linked to the promotion of cancer cell growth. The aim of this study was to evaluate the immunohistochemical expression of 5‐LOX pathway proteins in oesophageal adenocarcinoma and its premalignant lesion, Barrett’s metaplasia.
Methods and results: Tissue samples were collected at endoscopy from 16 patients with Barrett’s metaplasia and from seven with oesophageal adenocarcinoma; five proximal squamous oesophagus samples were used as controls. Immunohistochemical analyses were performed on stromal and epithelial areas with optimized concentrations of primary antibodies for 5‐LOX, 5‐LOX‐activating protein (FLAP), and the distal enzymes leukotriene (LT) A4 hydrolase (LTA4H) and LTC4 synthase (LTC4S). the diagnosis was histologically confirmed from adjacent sections by a gastrointestinal pathologist. Striking increases in the stromal immunoexpression of 5‐LOX (P = 0.041), FLAP (P = 0.038), LTA4H (P = 0.0008) and LTC4S (P = 0.036) were seen in adenocarcinoma tissue. Stromal FLAP and LTA4H immunostaining correlated with elevated neutrophil counts (P < 0.001). LTC4S was also notably overexpressed within epithelial cells in both Barrett’s metaplasia (P < 0.001) and adenocarcinoma (P < 0.01) tissue.
Conclusions: Key biosynthetic enzymes of the LTB4 and LTC4 biosynthetic pathways are incrementally expressed across the spectrum of squamous, Barrett’s metaplasia and oesophageal adenocarcinoma tissues, suggesting, for the first time, a role for both LT subfamilies in disease progression.
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Accepted/In Press date: May 2012
Published date: September 2012
Organisations:
Faculty of Medicine
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Local EPrints ID: 338094
URI: http://eprints.soton.ac.uk/id/eprint/338094
ISSN: 1365-2559
PURE UUID: bea2fd13-7a1b-4a9a-9a2a-48d633135599
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Date deposited: 09 May 2012 11:26
Last modified: 15 Mar 2024 02:56
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Author:
Philip C. Boger
Author:
James D. Shutt
Author:
James R. Neale
Author:
Adrian C. Bateman
Author:
Praful Patel
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