The Clinicopathological Significance of Tissue Levels of Hypoxia-inducible Factor-1α and Vascular Endothelial Growth Factor in Gastric Cancer

Background/Aims: Hypoxia-inducible factor-1 alpha (HIF-1 alpha) is a mediator of tumor progression. Vascular endothelial growth factor (VEGF) is the most potent angiogenic factor known to be induced by HIF-1 alpha. We investigated the clinicopathological significance of HIF-1 alpha and VEGF levels in biopsied gastric cancer tissue. Methods: Endoscopic biopsy specimens from 67 patients with gastric carcinoma who underwent surgery were available for this study. Semiquantitative RT-PCR was applied to biopsied tumors and normal tissues to determine the expressions of HIF-1 alpha and VEGF. The expression levels of HIF-1 alpha and VEGF were evaluated using the tumor:normal (T/N) ratios of HIF-1 alpha and VEGF mRNA. The clinicopathological variables were reviewed retrospectively. Results: The T/N ratios of HIF-1 alpha mRNA showed significant correlation with lymph-node metastases, distant metastases, stage, and recurrence within 3 years (p<0.05). The T/N ratios of VEGF mRNA showed significant correlation with lymph-node metastases and distant metastases (p<0.05). There was a significant correlation between the T/N ratios of HIF-1 alpha and VEGF mRNA (r=0.72, p<0.01). Conclusions: The increased expression of HIF-1 alpha and VEGF mRNA could reflect aggressive tumor behavior, including the recurrence of gastric cancer. Examination of HIF-1 alpha mRNA in biopsy specimens by RT-PCR assay might provide useful preoperative information on tumor aggressiveness. (Gut and Liver 2009;3:88-94)