Hypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas.

2.50
Hdl Handle:
http://hdl.handle.net/10541/71953
Title:
Hypoxia-inducible factor-1alpha expression in the gastric carcinogenesis sequence and its prognostic role in gastric and gastro-oesophageal adenocarcinomas.
Authors:
Griffiths, Ewen A; Pritchard, S A; Valentine, Helen R; Whitchelo, N; Bishop, P W; Ebert, M P; Price, Patricia M; Welch, I M; West, Catharine M L
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.
Affiliation:
Academic Radiation Oncology, Division of Cancer Studies, The University of Manchester, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK.
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
Journal:
British Journal of Cancer
Issue Date:
15-Jan-2007
URI:
http://hdl.handle.net/10541/71953
DOI:
10.1038/sj.bjc.6603524
PubMed ID:
17179985
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
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.en
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

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