Expression of hypoxia-inducible factor (HIF)-1α is associated with vascular endothelial growth factor expression and tumour anglogenesis in human oesophageal squamous cell carcinoma

The purpose of this study was to examine the relationship between hypoxia inducible factor (HIF)-1alpha expression, vascular endothelial growth factor (VEGF) expression, and tumour vascularity in squamous cell carcinoma of the oesophagus. Expression of HIF-1alpha and VEGF was examined in two oesophageal squamous cell carcinoma cell lines (TE2, TE3) and 82 archival surgical specimens of human oesophageal squamous cell carcinoma tissue. In both cell lines, the levels of HIF-1alpha protein and VEGF mRNA were increased under hypoxic conditions. Thirty-two of the 82 (39%) tumour specimens showed high levels of HIF-1alpha immunoreactivity in the nuclei and/or cytoplasm of cancer cells. HIF-1a expression cot-related significantly with venous invasion, VEGF expression, and microvessel density. Among the 47 patients who did not receive pre-operative chemotherapy, the outcome of those with high HIF-1alpha-expressing tumours was significantly poorer than that of those with low F[IF-1alpha-expressing turnours. These results suggest that HIF-1alpha and VEGF expression are important determinants of survival in squamous cell carcinoma of the oesophagus. (C) 2004 Elsevier Ltd. All rights reserved.