Show simple item record

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.
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
html.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.


This item appears in the following Collection(s)

Show simple item record