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

Research output: Contribution to journalArticle

  • External authors:
  • E. A. Griffiths
  • S. A. Pritchard
  • S. M. McGrath
  • H. R. Valentine
  • P. M. Price
  • I. M. Welch
  • C. M L West

Abstract

The study investigated hypoxia-associated markers (HIF-2α, 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)-2α 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-2α 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-2α was expressed in 63% of 177 resection specimens and at a high level in 44%. The median overall survival in patients with HIF-2α-expressing tumours was 22 (95% CI 18-26) months, whereas those with HIF-2α-negative tumours had a median survival of 37 (95% CI 29-44) months (P=0.015). Hypoxia-inducible factor-2α had no independent prognostic significance in multivariate analysis. In view of the lack of independent prognostic significance, HIF-2α has no role as a routine prognostic indicator. However, the high expression of HIF-2α suggests that it may be of value as a potential therapeutic target. © 2008 Cancer Research UK.

Bibliographical metadata

Original languageEnglish
Pages (from-to)965-973
Number of pages8
JournalBritish Journal of Cancer
Volume98
Issue number5
DOIs
Publication statusPublished - 11 Mar 2008