Expression Of HIF-1α In The Endometrial Cancer And Its Correlation With Tumor Angiogenesis

Hypoxia inducible factor - 1αlpha ( HIF - 1α) , is an essential regulatory protein for the adaptation of tumor cells to hypoxia, and regulates cell growth and causes a more malignant phenotype by increasing the expression of genes encoding angiogenic, metabolic and metastatic factors. HIF - 1α is a master tran-scriptional activator of oxygen - regulated genes and is constitutively upregulated in many tumor types. Vascular endothelial growth factor (VEGF) is one of the most important growth factors activating angiogensis of tumors. We studied relationship of HIF - 1α expression with VEGF and microvessel density ( MVD) in normal human endometrium, atypical hyperplasia of endometrium, and endome-triaal cancer.MethodsWe investigated expression of HIF - 1 alpha and VEGF by immunohisto-chemical method and counted MVD in specimens of endometrial cancer, atypical hyperplasia of endometrium and nomal endomedium.ResultsHIF - 1 alpha and VEGF are investigated. HIF - 1 alpha (63. 6% ) and VEGF(56.8%) is overexpressed in endometrial cancer. Positive expression of HIF - la is higher in the cancer of poor differentiation(85. 7% ) than that of good differentiation (43. 8%)(P<0.01). The positive expression of HIF - la was significantly higher in cases of FIGO II ~ IV than that of FIGO I (P <0. 05). MVD of endometrial cancer(45. 9 + 17. 5) is higher than that of normal endometrium( 17. 6 + 10. 9) (t = 5. 32, p < 0. 01). Using Spearman analysis, rs of HIF - la and VEGF is 0. 315, p <0. 05; rsof HIF - la and MVD is 0.579,p < 0.01; rsof VEGF and MVD is 0.607, p <0.01.ConclusionsThe positive rate of HIF -1α and VEGF gradually increased in normal human endometrium, atypical hyperplasia of endometrium and endometrial cancer, which may predict HIF -1αand its taget gene VEGF can play a very important role in the development of endometrial cancer.The positive expression of HIF - 1α increased from high differentiation to low differentiation, which indicates HIF -1α may devote to the genesis of endometrial cancer and be a marker of pathological grade of endometrial cancer.The expression of HIF - 1α are strongly correlated with VEGF and MVD. We can conclude that HIF - 1α is the regulatory link between tumor hypoxia and production of VEGF in endometrial cancer, thus establishing a biochemical pathway between tumor hypoxia and neoangiogenesis in this highly aggressive neoplasm. In all, HIF -1α can play important roles in genesis and development of endometrial carcinoma. It may become a new target of anti - tumor therapy.