International Journal of Clinical Oncology

, Volume 18, Issue 2, pp 293–304 | Cite as

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

  • Taro Isobe
  • Keishiro Aoyagi
  • Kikuo Koufuji
  • Kazuo Shirouzu
  • Akihiro Kawahara
  • Tomoki Taira
  • Masayoshi Kage
Original Article

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.

Keywords

HIF-1α VEGF Gastric cancer Clinicopathological factors 

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Copyright information

© Japan Society of Clinical Oncology 2012

Authors and Affiliations

  • Taro Isobe
    • 1
  • Keishiro Aoyagi
    • 1
  • Kikuo Koufuji
    • 1
  • Kazuo Shirouzu
    • 1
  • Akihiro Kawahara
    • 2
  • Tomoki Taira
    • 2
  • Masayoshi Kage
    • 2
  1. 1.Department of SurgeryKurume University School of MedicineKurumeJapan
  2. 2.Department of Diagnostic PathologyKurume University HospitalKurumeJapan

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