EXPRESSION OF HIF-1α,VEGF AND IGF-I IN ENDOMETRIAL CARCINOMA AND ITS CLINICAL SIGNIFICANCE

Objective To study the expression of hypoxia-inducible factor-1 alpha(HIF-1α),vascular endothelial growth factor(VEGF) and insulin-like growth factor-Ⅰ(IGF-Ⅰ) in endometrial carcinoma and to investigate the relationship between HIF-1α,VEGF and IGF-Ⅰ. Methods Immunohistochemistry PicTure~(TM) method was used to detect the expression of HIF-1α,VEGF and IGF-Ⅰ protein in 42 cases of endometrial adenocarcinoma,10 cases of atypical hyperplasia of endometrium and 20 cases of normal endometrium. Results HIF-1α,VEGF and IGF-Ⅰ were expressed in endometrial adenocarcinoma tissues,and the positive rates in atypical hyperplasia were 20%, 30% and 10%,respectively.The positive rates in endometrial carcinoma were 64.29%,61.90% and 59.52%.In contrast,normal endometrium did not express HIF-1α,VEGF or IGF-Ⅰ.The expressions of HIF-1α,VEGF and IGF-Ⅰ protein in endometrial adenocarcinoma were significantly higher than in normal endometrium tissues(χ~2=22.094-25.261,P0.01).The positive rate of HIF-1α was strongly associated with the clinical stage.The expression rates of HIF-1α protein in stages Ⅰ,Ⅱand Ⅲ were 42.11%,81.82% and 83.33%,respectively(χ~2=7.435,P0.05).There was no relationship between HIF-1α protein expression with age or histological grade(χ~2=0.036,0.634;P0.05).The positive rate of VEGF was strongly associated with the clinical stage.The expression rates of VEGF protein in stages Ⅰ,Ⅱand Ⅲwere 36.84%,81.81% and 75.00%(χ~2=6.578,P0.05).There was no relationship between VEGF protein expression and age or histological grade(χ~2=1.879,0.097;P0.05).There was no relationship between IGF-Ⅰprotein expression and age or clinical stage or histological grade(χ~2=0.190-0.791,P0.05).The expression of HIF-1α was positively associated with VEGF(r=(0.469),P0.01),The expression of IGFⅠwas positively associated with VEGF(r=0.452,P0.01),but there was no relationship between HIF-1α and IGF-Ⅰ(r=0.209,P0.05). Conclusion The overexpression of HIF-1α,VEGF and IGF-Ⅰ may play an important role in the carcinogenesis of endometrial carcinoma.The expression of HIF-1α,IGF-Ⅰ is positively associated with VEGF,but there is no relationship between HIF-1α and IGF-Ⅰ.The overexpression of HIF-1α and IGF-Ⅰ protein induces the tumor angiogenesis by activating the transcription of VEGF gene.They play important roles in the carcinogenesis of endometrial carcinoma.