Increasing expression of hypoxia-inducible proteins in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence.

2.50
Hdl Handle:
http://hdl.handle.net/10541/71929
Title:
Increasing expression of hypoxia-inducible proteins in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence.
Authors:
Griffiths, Ewen A; Pritchard, S A; McGrath, S M; Valentine, Helen R; Price, Patricia M; Welch, I M; West, Catharine M L
Abstract:
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)-1alpha, HIF-2alpha, 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-2alpha (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-2alpha was expressed late in the sequence and was only seen in dysplasia and adenocarcinoma. High HIF-2alpha expression was seen in 12 out of 20 Barrett's type adenocarcinoma. The late expression of HIF-2alpha 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.
Affiliation:
Academic Radiation Oncology, Division of Cancer Studies, Christie Hospital, The University of Manchester, Wilmslow Road, Withington, Manchester M20 4BX, UK.
Citation:
Increasing expression of hypoxia-inducible proteins in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. 2007, 96 (9):1377-83 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
7-May-2007
URI:
http://hdl.handle.net/10541/71929
DOI:
10.1038/sj.bjc.6603744
PubMed ID:
17437013
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorGriffiths, Ewen A-
dc.contributor.authorPritchard, S A-
dc.contributor.authorMcGrath, S M-
dc.contributor.authorValentine, Helen R-
dc.contributor.authorPrice, Patricia M-
dc.contributor.authorWelch, I M-
dc.contributor.authorWest, Catharine M L-
dc.date.accessioned2009-06-30T12:18:18Z-
dc.date.available2009-06-30T12:18:18Z-
dc.date.issued2007-05-07-
dc.identifier.citationIncreasing expression of hypoxia-inducible proteins in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence. 2007, 96 (9):1377-83 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid17437013-
dc.identifier.doi10.1038/sj.bjc.6603744-
dc.identifier.urihttp://hdl.handle.net/10541/71929-
dc.description.abstractHypoxia-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)-1alpha, HIF-2alpha, 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-2alpha (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-2alpha was expressed late in the sequence and was only seen in dysplasia and adenocarcinoma. High HIF-2alpha expression was seen in 12 out of 20 Barrett's type adenocarcinoma. The late expression of HIF-2alpha 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.en
dc.language.isoenen
dc.subjectOesophageal Canceren
dc.subject.meshAdenocarcinoma-
dc.subject.meshBarrett Esophagus-
dc.subject.meshBasic Helix-Loop-Helix Transcription Factors-
dc.subject.meshBiopsy-
dc.subject.meshDisease Progression-
dc.subject.meshEpithelial Cells-
dc.subject.meshEsophageal Diseases-
dc.subject.meshEsophageal Neoplasms-
dc.subject.meshEsophagus-
dc.subject.meshHypoxia-Inducible Factor 1, alpha Subunit-
dc.subject.meshImmunohistochemistry-
dc.subject.meshKi-67 Antigen-
dc.subject.meshMetaplasia-
dc.subject.meshReceptors, Erythropoietin-
dc.subject.meshReference Values-
dc.subject.meshVascular Endothelial Growth Factor A-
dc.titleIncreasing expression of hypoxia-inducible proteins in the Barrett's metaplasia-dysplasia-adenocarcinoma sequence.en
dc.typeArticleen
dc.contributor.departmentAcademic Radiation Oncology, Division of Cancer Studies, Christie Hospital, The University of Manchester, Wilmslow Road, Withington, Manchester M20 4BX, UK.en
dc.identifier.journalBritish Journal of Canceren

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.