Overexpression of hypoxia-inducible factor 1alpha and p53 is a marker for an unfavorable prognosis in gastric cancer.

PURPOSE: To investigate the effects of the expression of hypoxia-inducible factor 1alpha (HIF-1alpha) 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-1alpha and p53 proteins were studied by immunohistochemistry in 216 specimens of primary gastric cancer.

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

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