Correlation Of HIF-1α And VEGF Expression With The Angiogenesis Of Papillary Thyroid Carcinoma

Objective:By testing the expression of hypoxia-inducible factor-1α(HIF-1α), vascular endothelial growth factor(VEGF) proteins and assessing microvessel density(MVD) in papillary thyroid carcinoma(PTC),thyroid adenoma and normal thyroid tissue,we tried to reveal the relationship between the former factors and tumor biological characteristics,tumor angiogenesis.Method:1 We investigated the distribution and expression of HIF-1α,VEGF and assessed MVD in 43 PTCs,20 thyroid adenomas and 20 normal thyroid tissues by immunohistochemistry.And compared these former factors with clinical pathological datas of PTC.2 Western blot was used to detect the expression of HIF-1αin 10 PTCs,10 thyroid adenomas and 10 adjacent tissues of thyroid tumor.Result:1 HIF-1αprotein was mainly expressed in the cytoplasm of tumor cells and a small quantity of normal tissues.Statistical analysis revealed that HIF-1α-positive stained rate was significant higher in PTCs(67.4%) than that in thyroid adenomas(20.0%) and normal thyroid tissues(20.0%)(P＜0.01). There were significant differences when thyroid adenoma group and normal thyroid tissue group compared with PTC group(P＜0.01).2 VEGF protein was mainly expressed in the cytoplasm of tumor cells,some of the vascular endothelial cell could also be detected.Statistical analysis revealed that VEGF-positive stained rate was significant higher in PTCs (72.1%) than that in thyroid adenomas(25.0%) and normal thyroid tissues (15.0%)(P＜0.01).There were significant differences when thyroid adenoma group and normal thyroid tissue group compared with PTC group(P＜0.01).3 CD34 protein was expressed in the cytoplasm of vascular endothelial cell that were in the mesenchyme of both tumor cells and normal cells.Statistical analysis revealed that MVD was significant higher in PTCs(114.11±6.23) than that in thyroid adenomas(84.47±6.99) and normal thyroid tissues (49.83±6.12)(P＜0.01).There were significant differences when the groups compared with each other(P＜0.01).4 Statistical analysis revealed that the expression of HIF-1αprotein in PTCs had no significant relation with sex,age,tumor size or metastasis(P＞0.05), but it was correlated with lymph node metastasize,UICC stage(P＜0.05). Expression rate of HIF-1αprotein with lymph node metastasize(80.0%) was significant higher than that in without(50.0%)(P＜0.05).Accompany with the step up of UICC stage,the expression rates of HIF-1αprotein were rising(Ⅰ36.4%,Ⅱ60.0%,Ⅲ75.0%,Ⅳ92.9%)(P＜0.05).HIF-1α-positive stained rate was significant higher in advanced stage(Ⅲ,Ⅳ)(86.4%) than that in early stage(Ⅰ,Ⅱ)(47.6%)(P＜0.01).5 Statistical analysis revealed that the expression of VEGF protein in PTC had no significant relation with sex,age,tumor size or metastasis(P＞0.05),but it was correlated with lymph node metastasize,UICC stage(P＜0.05).Expression rate of VEGF protein with lymph node metastasize(84.0%) was significant higher than that in without(55.6%)(P＜0.05).Accompany with the step up of UICC stage,the expression rates of HIF-1αprotein were rising(Ⅰ36.4%,Ⅱ70.0%,Ⅲ75.0%,Ⅳ100.0%)(P＜0.01).There were significant differences when theⅣgroup compared with the others(P＜0.01).VEGF-positive stained rate was significant higher in advanced stage(Ⅲ,Ⅳ) (90.9%) than that in early stage(Ⅰ,Ⅱ)(52.4%)(P＜0.01).6 There was a positive relationship between HIF-1α-positive expression and VEGF-positive expression in PTC(r_s=0.567,P＜0.01).MVD in HIF-1α-positive stained PTC group(117.59±5.72) was significant higher in HIF-1α-negative stained group(109.20±1.98)(P＜0.01).MVD in VEGF-positive stained PTC group(116.98±5.98) was also significant higher in VEGF-negative stained group(109.31±2.21)(P＜0.01).In PTC with both HIF-1α-positive and VEGF-positive stained,the value of MVD was 122.17±4.97,but in both HIF-1α-negative and VEGF-negative stained tissues, the value was 108.21±0.98.The value of MVD was higher in the former than that in the latter(P＜0.01),accompany with the intensive expression of HIF-1αand VEGF protein.MVD was rising.7 Western blot analysis of HIF-1αprotein expression in PTC was significant increased(2.398±0.041)than that in thyroid adenoma(0.869±0.032) and thyroid normal tissue(0.199±0.027)(P＜0.01).There were significant differences when the groups compared with each other(P＜0.01).Conclusion:1 Increased expression of HIF-1α,VEGF protein and MVD in PTC indicated that HIF-1αand VEGF were closely correlated with carcinogenesis and metastasis of PTC.2 The expression rates of HIF-1αand VEGF protein were correlated with lymph node metastasize and UICC stage which manifest that both of them may have some effects in tumor malignancy and invasion.This may become an outcome indicator for PTC.3 The close relationship of HIF-1α,VEGF protein and MVD in PTC indicated that HIF-1αmay mediated angiogenesis by activating transcription of VEGF, newly growth microvascular may have provided an essensial enviroment for tumor cell growth,malignancy and invasion.