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

Date 28 September 2012
Event ESMO Congress 2012
Session Publication Only
Topics Gastric Cancer
Translational Research
Presenter Taro Isobe
Authors T. Isobe1, K. Aoyagi1, K. Hashimoto1, J. Kizaki1, M. Miyagi1, K. Koufuji1, T. Sasatomi2, K. Shirouzu1
  • 1Department Of Surgery, Kurume University School of Medicine, 8300011 - Kurume, Fukuoka/JP
  • 2Surgery, Kurume University School of Medicine, 8300011 - Kurume, Fukuoka/JP

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 over 60 genes recognized to control the delivery of oxygen and nutrients through the induction of angiogenesis and glycolysis under hypoxic condition. Therefore, Inhibition of expression of HIF-1α will be expected to the tumor specific molecular target-based therapy. In this study, we evaluated the significance of HIF-1α expression in relation to the clinicopatholgical factors, the prognosis, VEGF expression, and microvessel density (MVD) expressed as the mean count of CD34 immunostained vessels in gastric cancer.

Methods

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

Results

84(65.6%) of gastric cancer specimens were positive for HIF-1α expression. The multivariate analysis showed that the histology, depth of invasion, VEGF expression, and MVD were significantly associated with the HIF-1α expression. On relapse-free and overall survival curves, the HIF-1α negative group was significantly higher than the HIF-1α positive group. The HIF-1α expression was identified as 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 a poor prognostic factor for patients with gastric cancer and correlated with histology, depth of invasion, and VEGF.

Disclosure

All authors have declared no conflicts of interest.