Expression of hypoxia-inducible factor-1α and vessel endothelial growth factor in esophageal squamous cell carcinoma and clinico-pathological significance thereof

Abstract

To investigate the expression of hypoxia-inducible factor (HIF)-1alpha and vessel endothelial growth factor (VEGF) and their relations with the clinicopathological features of esophageal squamous cancer. Esophageal squamous cancer tissues and normal end squamous epithelium tissues were collected from 42 patients during operation. Real-time quantitative PCR was used to detect the mRNA expression of HIF-1alpha and VEGF and immunohistochemistry was used to detect the protein expression of HIF-1alpha and VEGF. The relations between the expression of HIF-1alpha, VEGF and depth of tumor invasion, histological grade, lymphatic invasion, and lymph node metastasis were evaluated. The HIF-1alpha mRNA expression level was 5.88 + 1.12 in the esophageal squamous cancer tissue, higher, but not significantly, than that in normal end squamous epithelium tissue 4.76 +/- 1.26 (P = 0.014). The VEGF mRNA expression level in the esophageal squamous cancer tissue was 12.79 +/- 2.51, higher, but not significantly, than that in the normal end squamous epithelium tissue (10.92 +/- 2.23, P = 0.010). The HIF-1alpha and VEGF protein positive rates in esophageal squamous cancer tissue were 50% (21/42) and 76% (32/42) respectively, significantly higher than those in the normal esophageal tissue [14% (6/42) and 33% (14/42) respectively, P = 0.001, P = 0.000]. The expression of HIF-1alpha mRNA and VEGF mRNA in the esophageal squamous cancer were correlated with lymph node metastasis (including lymphatic invasion) (P = 0.063 and P = 0.073 respectively). HIF-1alpha immunoreactivity was localized in the nucleus and/or cytoplasm of the cancer cells. The expression of HIF-1alpha protein was correlated with lymph node metastasis and histological grade (P = 0.013 and P = 0.028 respectively). No correlation was found between HIF-1alpha mRNA and VEGF protein. HIF-1alpha may be regulated at transcription and post-transcription levels in addition to protein level. It also plays an important role in lymphatic metastasis of esophageal squamous cancer and tumor malignancy degree. So HIF-1alpha and VEGF may serve as predictors of progression in esophageal squamous cell carcinoma and as potential targets for anti-angiogenesis therapy of esophageal squamous cell carcinoma.