Hypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas.
dc.contributor.author | Griffiths, Ewen A | |
dc.contributor.author | Pritchard, S A | |
dc.contributor.author | Valentine, Helen R | |
dc.contributor.author | Whitchelo, N | |
dc.contributor.author | Bishop, P W | |
dc.contributor.author | Ebert, M P | |
dc.contributor.author | Price, Patricia M | |
dc.contributor.author | Welch, I M | |
dc.contributor.author | West, Catharine M L | |
dc.date.accessioned | 2009-06-30T13:51:25Z | |
dc.date.available | 2009-06-30T13:51:25Z | |
dc.date.issued | 2007-01-15 | |
dc.identifier.citation | Hypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas. 2007, 96 (1):95-103 Br. J. Cancer | en |
dc.identifier.issn | 0007-0920 | |
dc.identifier.pmid | 17179985 | |
dc.identifier.doi | 10.1038/sj.bjc.6603524 | |
dc.identifier.uri | http://hdl.handle.net/10541/71953 | |
dc.description.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. | |
dc.language.iso | en | en |
dc.subject | Oesophageal Cancer | en |
dc.subject | Gastric Cancer | en |
dc.subject | Stomach Cancer | en |
dc.subject.mesh | Adenocarcinoma | |
dc.subject.mesh | Aged | |
dc.subject.mesh | Aged, 80 and over | |
dc.subject.mesh | Biopsy | |
dc.subject.mesh | Disease Progression | |
dc.subject.mesh | Esophageal Neoplasms | |
dc.subject.mesh | Female | |
dc.subject.mesh | Follow-Up Studies | |
dc.subject.mesh | Humans | |
dc.subject.mesh | Hypoxia-Inducible Factor 1, alpha Subunit | |
dc.subject.mesh | Immunohistochemistry | |
dc.subject.mesh | Male | |
dc.subject.mesh | Middle Aged | |
dc.subject.mesh | Multivariate Analysis | |
dc.subject.mesh | Neoplasm Invasiveness | |
dc.subject.mesh | Predictive Value of Tests | |
dc.subject.mesh | Prognosis | |
dc.subject.mesh | Staining and Labeling | |
dc.subject.mesh | Stomach Neoplasms | |
dc.subject.mesh | Survival Rate | |
dc.title | Hypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas. | en |
dc.type | Article | en |
dc.contributor.department | Academic Radiation Oncology, Division of Cancer Studies, The University of Manchester, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK. | en |
dc.identifier.journal | British Journal of Cancer | en |
html.description.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. |