[Relationship of hypoxia-inducible factor 1 alpha (HIF-1alpha) gene expression with vascular endothelial growth factor (VEGF) and microvessel density (MVD) in human colorectal adenoma and adenocarcinoma].

Background & Objective: Hypoxia-inducible factor-1 alpha (HIF-1alpha), a transcriptional factor response to hypoxia plays an important role in tumor angiogenesis. This study was designed to examine the expression of HIF-1alpha gene and its relationship with vascular endothelial growth factor (VEGF) protein and microvessel density (MVD).

Methods: HIF-1alpha gene expression was analyzed using in situ hybridization, and VEGF expression levels were determined by immunohistochemistry in colorectal adenomas and primary colorectal adenocarcinomas. Microvessel density (MVD) was determined by anti-CD34 immunostaining.

Results: Positive expression of HIF-1alpha mRNA were found in 67.8% (42/62) of the colorectal adenocarcinomas and 44.4% (8/18) of the adenomas. The mean percentage of HIF-1alpha mRNA positive cells increased gradually with the development from Dukes'stage A to stage C+D (P< 0.05). The frequencies of HIF-1alpha positive cells in pathologic stage of the specimens were as follows: adenoma 8%, Dukes A 14%, Dukes B 23%, Dukes C+D 35%. The positive expression rate of VEGF protein in colorectal adenocarcinoma group was significantly higher than that in colorectal adenoma group (59.7% vs 33.3%,P< 0.05). During colorectal tumor progression, the expression of HIF-1alphamRNA was positively correlated with the VEGF protein expression and MVD (r(s) = 0.768 P< 0.01 and r(s) = 0.683 P< 0.05, respectively).

Conclusion: These results suggest that tumor angiogenesis induced by HIF-1alpha mRNA and VEGF protein might play an important role in tumorigenesis of colorectal adenoma and progression of colorectal cancer.