Expression of vascular endothelial growth factor and hypoxia inducible factor-1alpha in cervical neoplasia.

Altered angiogenesis is an important phenotype of high-grade cervical lesions and invasive cervical carcinomas. Many researchers, including us, have shown that oncoproteins of human papillomavirus could enhance the vascular endothelial growth factor (VEGF) expression. We investigated the change in VEGF and hypoxia-inducible factor-1alpha (HIF-1alpha) expression patterns that occur during the carcinogenesis and progression of cervical cancer. Expressions of HIF-1alpha and VEGF were evaluated by immunohistochemistry using paraffin-embedded specimens obtained from 41 patients with a normal cervix, 39 patients with cervical intraepithelial neoplasia (CIN 1, 10; CIN 2/3, 29), and 36 patients with cervical cancer. The VEGF and HIF-1alpha expressions were higher in CIN and invasive cancer than in normal cervix (P= 0.021, P < 0.001, respectively). It is interesting to note that there was no significant difference in VEGF and HIF-1alpha overexpressions between CIN 2/3 and cervical cancer and between nonmetastatic and metastatic cancers. In addition, there was a significant correlation between the immunohistochemical score of HIF-1alpha and that of VEGF expression (Spearman's correlation coefficient 0.275, P= 0.003, n= 116). Taken together, the results of our study suggest that expressions of VEGF and HIF-1alpha could be involved in cervical carcinogenesis. In addition, the weak correlation between VEGF and HIF-1alpha expressions suggests that regulatory mechanisms other than HIF-1alpha may be involved in the expression of VEGF during cervical carcinogenesis.