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Increasing expression of hypoxia-inducible proteins in the Barrett's metaplasia–dysplasia–adenocarcinoma sequence
Hypoxia-associated markers are involved in the progression of several malignancies, but are relatively unstudied in Barrett's carcinogenesis. Our aim was to assess the immunohistochemical expression of hypoxia-inducible factor (HIF)-1α, HIF-2α, erythropoietin (Epo), Epo receptor (Epo-R), Glut-1...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2007
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360174/ https://www.ncbi.nlm.nih.gov/pubmed/17437013 http://dx.doi.org/10.1038/sj.bjc.6603744 |
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author | Griffiths, E A Pritchard, S A McGrath, S M Valentine, H R Price, P M Welch, I M West, C M L |
author_facet | Griffiths, E A Pritchard, S A McGrath, S M Valentine, H R Price, P M Welch, I M West, C M L |
author_sort | Griffiths, E A |
collection | PubMed |
description | Hypoxia-associated markers are involved in the progression of several malignancies, but are relatively unstudied in Barrett's carcinogenesis. Our aim was to assess the immunohistochemical expression of hypoxia-inducible factor (HIF)-1α, HIF-2α, erythropoietin (Epo), Epo receptor (Epo-R), Glut-1 and vascular endothelial growth factor (VEGF) along with Ki67/MIB-1 in the Barrett's metaplasia–dysplasia–adenocarcinoma sequence. Endoscopic biopsies of normal squamous epithelium (NSE) (n=20), columnar-lined oesophagus (CLO) (n=15), CLO with intestinal metaplasia (n=20), dysplasia (n=17) and Barrett's type adenocarcinoma (n=20) were obtained. Immunohistochemistry was performed on the paraffin-embedded tissue. A score was calculated for each marker (range 0−300) by multiplying intensity (none 0, weak 1, moderate 2, strong 3) by percentage of expression (range 0–100). Significant increases in the expression of HIF-2α (P=0.014), VEGF (P<0.0001), Epo-R (P<0.0001) and Ki67 (P<0.0001) were found as tissue progressed from NSE to adenocarcinoma. HIF-2α was expressed late in the sequence and was only seen in dysplasia and adenocarcinoma. High HIF-2α expression was seen in 12 out of 20 Barrett's type adenocarcinoma. The late expression of HIF-2α in the Barrett's carcinogenesis sequence and its high expression in adenocarcinoma suggest that it is worth further investigation as a marker of disease progression and therapeutic target. |
format | Text |
id | pubmed-2360174 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2007 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-23601742009-09-10 Increasing expression of hypoxia-inducible proteins in the Barrett's metaplasia–dysplasia–adenocarcinoma sequence Griffiths, E A Pritchard, S A McGrath, S M Valentine, H R Price, P M Welch, I M West, C M L Br J Cancer Molecular Diagnostics Hypoxia-associated markers are involved in the progression of several malignancies, but are relatively unstudied in Barrett's carcinogenesis. Our aim was to assess the immunohistochemical expression of hypoxia-inducible factor (HIF)-1α, HIF-2α, erythropoietin (Epo), Epo receptor (Epo-R), Glut-1 and vascular endothelial growth factor (VEGF) along with Ki67/MIB-1 in the Barrett's metaplasia–dysplasia–adenocarcinoma sequence. Endoscopic biopsies of normal squamous epithelium (NSE) (n=20), columnar-lined oesophagus (CLO) (n=15), CLO with intestinal metaplasia (n=20), dysplasia (n=17) and Barrett's type adenocarcinoma (n=20) were obtained. Immunohistochemistry was performed on the paraffin-embedded tissue. A score was calculated for each marker (range 0−300) by multiplying intensity (none 0, weak 1, moderate 2, strong 3) by percentage of expression (range 0–100). Significant increases in the expression of HIF-2α (P=0.014), VEGF (P<0.0001), Epo-R (P<0.0001) and Ki67 (P<0.0001) were found as tissue progressed from NSE to adenocarcinoma. HIF-2α was expressed late in the sequence and was only seen in dysplasia and adenocarcinoma. High HIF-2α expression was seen in 12 out of 20 Barrett's type adenocarcinoma. The late expression of HIF-2α in the Barrett's carcinogenesis sequence and its high expression in adenocarcinoma suggest that it is worth further investigation as a marker of disease progression and therapeutic target. Nature Publishing Group 2007-05-07 2007-04-17 /pmc/articles/PMC2360174/ /pubmed/17437013 http://dx.doi.org/10.1038/sj.bjc.6603744 Text en Copyright © 2007 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Molecular Diagnostics Griffiths, E A Pritchard, S A McGrath, S M Valentine, H R Price, P M Welch, I M West, C M L Increasing expression of hypoxia-inducible proteins in the Barrett's metaplasia–dysplasia–adenocarcinoma sequence |
title | Increasing expression of hypoxia-inducible proteins in the Barrett's metaplasia–dysplasia–adenocarcinoma sequence |
title_full | Increasing expression of hypoxia-inducible proteins in the Barrett's metaplasia–dysplasia–adenocarcinoma sequence |
title_fullStr | Increasing expression of hypoxia-inducible proteins in the Barrett's metaplasia–dysplasia–adenocarcinoma sequence |
title_full_unstemmed | Increasing expression of hypoxia-inducible proteins in the Barrett's metaplasia–dysplasia–adenocarcinoma sequence |
title_short | Increasing expression of hypoxia-inducible proteins in the Barrett's metaplasia–dysplasia–adenocarcinoma sequence |
title_sort | increasing expression of hypoxia-inducible proteins in the barrett's metaplasia–dysplasia–adenocarcinoma sequence |
topic | Molecular Diagnostics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360174/ https://www.ncbi.nlm.nih.gov/pubmed/17437013 http://dx.doi.org/10.1038/sj.bjc.6603744 |
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