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British Journal of Cancer (2008) 98, 965-973.
doi:10.1038/sj.bjc.6604210 www.bjcancer.com Published online 19 February 2008
Hypoxia-associated markers in gastric carcinogenesis and HIF-2
in gastric and gastro-oesophageal cancer prognosisE A Griffiths1,2, S A Pritchard3, S M McGrath3, H R Valentine1, P M Price1, I M Welch2 and C M L West1
1Academic Department of Radiation Oncology, School of Cancer & Imaging Sciences, The University of Manchester, Christie Hospital, Wilmslow Road, Withington, Manchester M20 4BX, UK
2Department of Gastrointestinal Surgery, South Manchester University Hospitals NHS Trust, Manchester M23 9LT, UK
3Department of Histopathology, South Manchester University Hospitals NHS Trust, Manchester M23 9LT, UK
Correspondence to: Dr CML West, Academic Radiation Oncology, The University of Manchester, Christie Hospital, Wilmslow Road, Withington, Manchester, M20 4BX, UK. E-mail: Catharine.West@manchester.ac.uk
Received 4 October 2007; revised 3 January 2008; accepted 3 January 2008; published online 19 February 2008
The study investigated hypoxia-associated markers (HIF-2
, 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)-2 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-2 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-2 was expressed in 63% of 177 resection specimens and at a high level in 44%. The median overall survival in patients with HIF-2-expressing tumours was 22 (95% CI 18-26) months, whereas those with HIF-2-negative tumours had a median survival of 37 (95% CI 29-44) months (P=0.015). Hypoxia-inducible factor-2 had no independent prognostic significance in multivariate analysis. In view of the lack of independent prognostic significance, HIF-2 has no role as a routine prognostic indicator. However, the high expression of HIF-2 suggests that it may be of value as a potential therapeutic target.Keywords: gastric cancer; gastro-oesophageal junction tumours; HIF-2
; hypoxia; carcinogenesisback to top  |
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