Hypoxia-associated markers in gastric carcinogenesis and HIF-2alpha in gastric and gastro-oesophageal cancer prognosis.

2.50
Hdl Handle:
http://hdl.handle.net/10541/67980
Title:
Hypoxia-associated markers in gastric carcinogenesis and HIF-2alpha in gastric and gastro-oesophageal cancer prognosis.
Authors:
Griffiths, Ewen A; Pritchard, S A; McGrath, S M; Valentine, Helen R; Price, Patricia M; Welch, I M; West, Catharine M L
Abstract:
The study investigated hypoxia-associated markers (HIF-2alpha, Epo, Epo-R, Glut-1 and VEGF) along with Ki-67 in a gastric carcinogenesis model, and the prognostic significance of hypoxia-inducible factor (HIF)-2alpha in surgically treated gastro-oesophageal cancer. Protein expression was examined using immunohistochemistry on formalin-fixed, paraffin-embedded biopsies of normal mucosa (n=20), Helicobacter pylori-associated gastritis (n=24), intestinal metaplasia (n=24), dysplasia (n=12) and intestinal (n=19) and diffuse (n=21) adenocarcinoma. Relationships between HIF-2alpha expression and prognosis were assessed in resection specimens from 177 patients with gastric and gastro-oesophageal junction adenocarcinoma. Expression of all markers increased with progression along the gastric carcinogenesis sequence (P=0.0001). Hypoxia-inducible factor-2alpha was expressed in 63% of 177 resection specimens and at a high level in 44%. The median overall survival in patients with HIF-2alpha-expressing tumours was 22 (95% CI 18-26) months, whereas those with HIF-2alpha-negative tumours had a median survival of 37 (95% CI 29-44) months (P=0.015). Hypoxia-inducible factor-2alpha had no independent prognostic significance in multivariate analysis. In view of the lack of independent prognostic significance, HIF-2alpha has no role as a routine prognostic indicator. However, the high expression of HIF-2alpha suggests that it may be of value as a potential therapeutic target.
Affiliation:
Academic Department of Radiation Oncology, School of Cancer & Imaging Sciences, The University of Manchester, Christie Hospital, Wilmslow Road, Withington, Manchester M20 4BX, UK.
Citation:
Hypoxia-associated markers in gastric carcinogenesis and HIF-2alpha in gastric and gastro-oesophageal cancer prognosis. 2008, 98 (5):965-73 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
11-Mar-2008
URI:
http://hdl.handle.net/10541/67980
DOI:
10.1038/sj.bjc.6604210
PubMed ID:
18283323
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications ; Academic Department of Radiation Oncology - ADRO

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.accessioned2009-05-12T16:56:10Z-
dc.date.available2009-05-12T16:56:10Z-
dc.date.issued2008-03-11-
dc.identifier.citationHypoxia-associated markers in gastric carcinogenesis and HIF-2alpha in gastric and gastro-oesophageal cancer prognosis. 2008, 98 (5):965-73 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid18283323-
dc.identifier.doi10.1038/sj.bjc.6604210-
dc.identifier.urihttp://hdl.handle.net/10541/67980-
dc.description.abstractThe study investigated hypoxia-associated markers (HIF-2alpha, Epo, Epo-R, Glut-1 and VEGF) along with Ki-67 in a gastric carcinogenesis model, and the prognostic significance of hypoxia-inducible factor (HIF)-2alpha in surgically treated gastro-oesophageal cancer. Protein expression was examined using immunohistochemistry on formalin-fixed, paraffin-embedded biopsies of normal mucosa (n=20), Helicobacter pylori-associated gastritis (n=24), intestinal metaplasia (n=24), dysplasia (n=12) and intestinal (n=19) and diffuse (n=21) adenocarcinoma. Relationships between HIF-2alpha expression and prognosis were assessed in resection specimens from 177 patients with gastric and gastro-oesophageal junction adenocarcinoma. Expression of all markers increased with progression along the gastric carcinogenesis sequence (P=0.0001). Hypoxia-inducible factor-2alpha was expressed in 63% of 177 resection specimens and at a high level in 44%. The median overall survival in patients with HIF-2alpha-expressing tumours was 22 (95% CI 18-26) months, whereas those with HIF-2alpha-negative tumours had a median survival of 37 (95% CI 29-44) months (P=0.015). Hypoxia-inducible factor-2alpha had no independent prognostic significance in multivariate analysis. In view of the lack of independent prognostic significance, HIF-2alpha has no role as a routine prognostic indicator. However, the high expression of HIF-2alpha suggests that it may be of value as a potential therapeutic target.en
dc.language.isoenen
dc.subjectGastric Canceren
dc.subjectOesophageal Canceren
dc.subjectStomach Canceren
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAnoxia-
dc.subject.meshBasic Helix-Loop-Helix Transcription Factors-
dc.subject.meshBiological Markers-
dc.subject.meshEsophageal Neoplasms-
dc.subject.meshFemale-
dc.subject.meshGlucose Transporter Type 1-
dc.subject.meshHumans-
dc.subject.meshHypoxia-Inducible Factor 1, alpha Subunit-
dc.subject.meshImmunohistochemistry-
dc.subject.meshKi-67 Antigen-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshPrognosis-
dc.subject.meshStomach Neoplasms-
dc.subject.meshVascular Endothelial Growth Factor A-
dc.titleHypoxia-associated markers in gastric carcinogenesis and HIF-2alpha in gastric and gastro-oesophageal cancer prognosis.en
dc.typeArticleen
dc.contributor.departmentAcademic Department of Radiation Oncology, School of Cancer & Imaging Sciences, The University of Manchester, Christie Hospital, Wilmslow Road, Withington, Manchester M20 4BX, UK.en
dc.identifier.journalBritish Journal of Canceren

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