Hypoxia frequently occurs in various
solid tumors, thereby accelerating cancer progression and treatment resistance. Hypoxia-inducible factor-1alpha (HIF-1alpha) plays a central role in
tumor hypoxia by up-regulating the
gene expression related to
angiogenesis, cancer invasion and anti-apoptosis. The present study immunohistochemically investigated HIF-1alpha expression in 63
gastric cancer specimens. Those specimens were obtained from 44 patients that received
5-FU chemotherapy post-operatively whereas the remaining 19 patients did not. The
immunostaining pattern of HIF-1alpha was classified into 3 patterns: diffuse-positive within the
tumor (DP), positive at the invasive front of the
tumor (FP) and negative (N). Thirty-six of 63 (57.1%) patients exhibited DP, 24 (38.1%) revealed FP and the remaining 3 (4.8%) patients were judged as N. The HIF-1alpha expression pattern grouped into DP and FP/N
correlated with the clinicopathological factors and survival. As a result, the HIF-1alpha expression did not show a significant
correlation with the clinicopathological factors, such as the depth of invasion,
lymph node metastasis and
tumor stage, nor patient survival in the 63 patients. However, in the 44 patients that underwent
chemotherapy, patients with the FP/N pattern showed longer survival than those with the DP pattern. On the other
hand, no significant difference in survival was found between the 2 patterns among 19 patients without the
chemotherapy. These results indicated that the diffuse expression of HIF-1alpha in
gastric tumors might lead to
drug resistance against
adjuvant chemotherapy using
5-FU. In conclusion, the assessment of the HIF-1alpha expression in the resected tissues might predict the
drug response to adjuvant
5-FU chemotherapy in advanced
gastric cancer patients.
