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Overexpression of Hypoxia-Inducible Factor 1 and p53 Is a Marker for an Unfavorable Prognosis in Gastric Cancer

Authors' Affiliations: ¹ Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka and ² Department of Surgery, Saga Prefectural Hospital Koseikan, Saga, Japan

Requests for reprints: Yoshihiro Kakeji, Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Maidashi 3-1-1, Higashi-ku, Fukuoka 812-8582, Japan. Phone: 81-92-642-5466; Fax: 81-92-642-5482; E-mail: kakeji{at}surg2.med.kyushu-u.ac.jp.

Purpose: To investigate the effects of the expression of hypoxia-inducible factor 1 (HIF-1) and p53 on the prognosis of human gastric cancer, the clinicopathologic characteristics of the tumors and the clinical outcome were analyzed.

Experimental Design: The expressions of HIF-1 and p53 proteins were studied by immunohistochemistry in 216 specimens of primary gastric cancer.

Results: HIF-1(+)/p53(+) tumors more frequently showed an undifferentiated type, an infiltrative growth appearance, and an invasive lymphatic involvement compared with HIF-1(–)/p53(–) tumors. HIF-1(+)/p53(+) tumors also had more lymph node metastasis compared with HIF-1(–)/p53(–) tumors. When stratified for HIF-1 and p53 positivity, the patients who were p53-negative and HIF-1-negative had the most favorable prognosis, whereas patients who were p53-positive and HIF-1-positive had the worst prognosis (P = 0.0018). Using a multivariate Cox regression analysis, the depth of invasion, lymph node metastasis, and HIF-1 positivity were all found to be independent prognostic factors in patients with gastric cancer.

Conclusion: Thus, HIF-1 is considered to be a useful independent prognostic factor in gastric cancer, and the combination of a HIF-1 protein overexpression with nonfunctional p53 tends to indicate a dismal prognosis.

Commentary

Hypoxia-Inducible Factor-1 and p53: Friends, Acquaintances, or Strangers?

Ester M. Hammond and Amato J. Giaccia
Clin. Cancer Res. 2006 12: 5007-5009. [Full Text] [PDF]

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				E. M. Hammond and A. J. Giaccia Hypoxia-Inducible Factor-1 and p53: Friends, Acquaintances, or Strangers? Clin. Cancer Res., September 1, 2006; 12(17): 5007 - 5009. [Full Text] [PDF]