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dc.contributor.authorGriffiths, Ewen A
dc.contributor.authorPritchard, S A
dc.contributor.authorValentine, Helen R
dc.contributor.authorWhitchelo, N
dc.contributor.authorBishop, P W
dc.contributor.authorEbert, M P
dc.contributor.authorPrice, Patricia M
dc.contributor.authorWelch, I M
dc.contributor.authorWest, Catharine M L
dc.date.accessioned2009-06-30T13:51:25Z
dc.date.available2009-06-30T13:51:25Z
dc.date.issued2007-01-15
dc.identifier.citationHypoxia-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. Canceren
dc.identifier.issn0007-0920
dc.identifier.pmid17179985
dc.identifier.doi10.1038/sj.bjc.6603524
dc.identifier.urihttp://hdl.handle.net/10541/71953
dc.description.abstractHypoxia-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.isoenen
dc.subjectOesophageal Canceren
dc.subjectGastric Canceren
dc.subjectStomach Canceren
dc.subject.meshAdenocarcinoma
dc.subject.meshAged
dc.subject.meshAged, 80 and over
dc.subject.meshBiopsy
dc.subject.meshDisease Progression
dc.subject.meshEsophageal Neoplasms
dc.subject.meshFemale
dc.subject.meshFollow-Up Studies
dc.subject.meshHumans
dc.subject.meshHypoxia-Inducible Factor 1, alpha Subunit
dc.subject.meshImmunohistochemistry
dc.subject.meshMale
dc.subject.meshMiddle Aged
dc.subject.meshMultivariate Analysis
dc.subject.meshNeoplasm Invasiveness
dc.subject.meshPredictive Value of Tests
dc.subject.meshPrognosis
dc.subject.meshStaining and Labeling
dc.subject.meshStomach Neoplasms
dc.subject.meshSurvival Rate
dc.titleHypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas.en
dc.typeArticleen
dc.contributor.departmentAcademic Radiation Oncology, Division of Cancer Studies, The University of Manchester, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK.en
dc.identifier.journalBritish Journal of Canceren
html.description.abstractHypoxia-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.


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