Login
- Document type:
- Journal Article; Research Support, Non-U.S. Gov't; Article
- Author(s):
- Griffiths, EA; Pritchard, SA; Valentine, HR; Whitchelo, N; Bishop, PW; Ebert, MP; Price, PM; Welch, IM; West, CM
- Title:
- Hypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas.
- Abstract:
- Hypoxia-inducible factor-1 (HIF-1)alpha expression was studied in the gastric carcinogenesis sequence and as a prognostic factor in surgically resected gastric and gastro-oesophageal junction tumours. Protein expression was examined using immunohistochemistry on formalin-fixed 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. The relationship between HIF-1alpha expression and prognosis was assessed in resection specimens from 177 patients with gastric and gastro-oesophageal junction adenocarcinoma. Hypoxia-inducible factor-1alpha expression was not observed in normal gastric mucosa but increased in density (P<0.01) and intensity (P<0.01) with progression from H. pylori-associated gastritis, intestinal metaplasia, dysplasia to adenocarcinoma. The pattern of staining in the resection specimens was focally positive in 49 (28%) and at the invasive tumour edge in 41 (23%). Invasive edge expression was associated with lymph node metastases (P=0.034), advanced TNM stage (P=0.001) and was an adverse prognostic factor for cancer-specific survival (P=0.019). In univariate analysis and in comparison with tumours not expressing HIF-1alpha, invasive edge staining was associated with a hazard ratio of 1.6 (95% CI 1.0-2.5) and focally positive staining a hazard ratio of 0.7 (95% CI 0.5-1.2). Hypoxia-inducible factor-1alpha lost prognostic significance in multivariate analysis. The results suggest HIF-1alpha is involved in gastric carcinogenesis and disease progression, but is only a weak prognostic factor for survival.
- Journal title abbreviation:
- Br J Cancer
- Year:
- 2007
- Journal volume:
- 96
- Journal issue:
- 1
- Pages contribution:
- 95-103
- Language:
- eng
- Fulltext / DOI:
- doi:10.1038/sj.bjc.6603524
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/17179985
- Print-ISSN:
- 0007-0920
- TUM Institution:
- II. Medizinische Klinik und Poliklinik (Gastroenterologie)
BibTeX