Expression of Hypoxia-inducible Factor-1 alpha Protein in Stages I and II Squamous Cell Carcinomas of the Uterine Cervix: Relationship with p53 Protein and VEGF Expressions

ABSTRACT

BACKGROUND: Under hypoxia, hypoxia-inducible factor-1alpha (HIF-1alpha) is known to activate the expression of various genes, including angiogenesis-related genes. The aim of this study was to evaluate the expression of HIF-1alpha protein and its relationship with p53 protein expression and angiogenesis in the squamous cell carcinoma (SCC) of the uterine cervix. METHODS: Using immunohistochemical methods, the expression of HIF-1alpha protein, p53 protein, vascular endothelial growth factor (VEGF), and microvessel count were evaluated in seventy cases of FIGO stages I and II SCC; and their results were compared with age, stage, and pelvic lymph node metastasis. RESULTS: Positive nuclear staining for HIF-1alpha protein was noted in 19 cases (27.1%). Carcinoma in situ or dysplastic lesions also revealed positive nuclear reaction along the lower part of the epithelium. The expression of HIF-1alpha protein was significantly related with those of p53 protein and VEGF (p<0.05), but not with other clinicopathologic parameters. The microvessel count showed a significant difference regarding stage and VEGF expression (pand<0.05). CONCLUSION: These findings suggest that HIF-1alpha expression in SCCs of the uterine cervix might be the early event of carcinogenesis and could be associated with p53 protein and VEGF expression. However, the prognostic significance of HIF-1alpha expression in stages I and II SCCs is undetermined.