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International Journal of Clinical Oncology
Published in: International Journal of Clinical Oncology 2/2013

01-04-2013 | Original Article

Clinicopathological significance of hypoxia-inducible factor-1 alpha (HIF-1α) expression in gastric cancer

Authors: Taro Isobe, Keishiro Aoyagi, Kikuo Koufuji, Kazuo Shirouzu, Akihiro Kawahara, Tomoki Taira, Masayoshi Kage

Published in: International Journal of Clinical Oncology | Issue 2/2013

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Abstract

Background

Hypoxia is a common feature of rapidly growing solid tumors. Therefore, cellular adaptation to hypoxia and altered glucose metabolism are fundamental to the biology of cancer cells. Hypoxia-inducible factor-1α (HIF-1α) is a transcription factor for more than 60 genes recognized to control the delivery of oxygen and nutrients through the induction of angiogenesis and glycolysis under hypoxic conditions. Therefore, inhibition of the expression of HIF-1α can be expected to be potentially tumor-specific molecular target-based therapy. In this study, we evaluated the significance of HIF-1α expression in relationship to clinicopathological factors, prognosis, vascular endothelial growth factor (VEGF) expression, and microvessel density (MVD).

Methods

Paraffin-embedded tumor specimens from 128 patients who underwent gastrectomy at Kurume University from 2004 to 2005 were used to assess the clinical significance of HIF-1α expression. We used the ABC method to perform an immunohistochemical analysis of the HIF-1α and VEGF expression.

Results

Eighty-four (65.6%) of gastric cancer specimens were positive for HIF-1α expression. Multivariate analysis showed that histology, depth of invasion, VEGF expression, and MVD were significantly associated with HIF-1α expression. On relapse-free and overall survival curves, the HIF-1α-negative group was significantly higher than the HIF-1α-positive group. Moreover, HIF-1α(+)/VEGF(+) patients had the worst prognosis. HIF-1α expression was identified as a significant predictor of relapse-free survival and overall survival by multivariate Cox’s proportional hazard analyses.

Conclusion

Overexpression of HIF-1α was found to be an indicator of poor prognosis for patients with gastric cancer and was significantly correlated with histology, depth of invasion, VEGF, and MVD.
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Metadata
Title
Clinicopathological significance of hypoxia-inducible factor-1 alpha (HIF-1α) expression in gastric cancer
Authors
Taro Isobe
Keishiro Aoyagi
Kikuo Koufuji
Kazuo Shirouzu
Akihiro Kawahara
Tomoki Taira
Masayoshi Kage
Publication date
01-04-2013
Publisher
Springer Japan
Published in
International Journal of Clinical Oncology / Issue 2/2013
Print ISSN: 1341-9625
Electronic ISSN: 1437-7772
DOI
https://doi.org/10.1007/s10147-012-0378-8

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