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

Purpose: To investigate the effects of the expression of hypoxia-inducible factor 1α (HIF-1α) 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-1α and p53 proteins were studied by immunohistochemistry in 216 specimens of primary gastric cancer. Results: HIF-1α(+)/p53(+) tumors more frequently showed an undifferentiated type, an infiltrative growth appearance, and an invasive lymphatic involvement compared with HIF-1α(−)/p53(−) tumors. HIF-1α(+)/p53(+) tumors also had more lymph node metastasis compared with HIF-1α(−)/p53(−) tumors. When stratified for HIF-1α and p53 positivity, the patients who were p53-negative and HIF-1α-negative had the most favorable prognosis, whereas patients who were p53-positive and HIF-1α-positive had the worst prognosis ( P = 0.0018). Using a multivariate Cox regression analysis, the depth of invasion, lymph node metastasis, and HIF-1α positivity were all found to be independent prognostic factors in patients with gastric cancer. Conclusion: Thus, HIF-1α is considered to be a useful independent prognostic factor in gastric cancer, and the combination of a HIF-1α protein overexpression with nonfunctional p53 tends to indicate a dismal prognosis.