Expression Of HIF-1α、VEGF And MMP-9in Endometrioida Denocarcinoma And Its Clinical Significance

Objective:To study the expressions of HIF-1α, VEGF and MMP-9in endometrioid adenocarcinoma and their clinicopathological relationship, and investigate the impact of HIF-1α、VEGF、and MMP-9, and the relation with HIF-1α、VEGF、and MMP-9protein over expression on the development and biological behavior of endometrial carcinoma.Methods:Expressions of HIF-1α, VEGF and MMP-9in60cases of endometrioid adenocarcinoma and30cases of benign endometrial controls were detected, according to FIGO2000endometrial carcinoma operation-the pathological stage:Ⅰ (17cases), Ⅱ (21cases) and Ⅲ (23patients). Pathological grade is divided into well-differentiation (G1)30cases, moderate differentiation (G2)16cases and poor differentiation (G3)14cases. Endometrioid adenocarcinoma and benign endometrial tissue microarray were constructed. Application of SPSS (11FOR WINDOWS) software package was used for statistical analysis, and PV-9000two-step method for immunohistochemical staining. Using X2test, correlation analysis of three indexes by Spearman correlation test, the changes of expression of different tissue types, age, operation and pathological staging, lymph node metastasis were analized as well as the relationship between the expressions of three gene in endometrial adenocarcinoma and its clinicopathological features.Results:The positive rate of HIF-1α, VEGF and MMP-9in endometrial adenocarcinoma was significantly higher than that in the benign endometrium (P<0.05). HIF-la in the control group and the endometrial carcinoma expression positive rates were43.30%,73.30%,(P<0.01). The positive expression of HIF-la protein rate in stage I35.29%(6/17), II71.43%(15/21) and Ⅲ78.26%(18/23), there was a significant difference among the three (P<0.05). The expression of HIF-la was not related age (P>0.05); the positive rate of lymph node metastasis in endometrial cancer cases (85.70%) was significantly higer than those without lymph node metastasis (56.00%)(P<0.05),and nothing to do with the pathological grade (P>0.05).VEGF expression rates in the control group and the endometrial carcinoma were50.00%and80.00%, without significant difference (P<0.05); the positive expression rates of VEGF in stages were Ⅰ44.44%(8/18), Ⅱ80%(16/20) and Ⅲ86.36%(19/22), and there was a significant difference between the three (P<0.05). VEGF expression in the lymph node metastasis cases (88.57%) was higher than those of without lymph node metastasis cases (52.00%) P<0.05, and no difrencese were found in age of onset (P>0.05) and pathological grade groups.MMP-9expression was significantly higher in the endometrium cancer casese (80.00%) than that of benign group,(46.67%, P<0.01) as well as in lymph node metastasis (91.43%) than that of none lymph node metastasis casese (48.00%P<0.05), and there was difference of MMP-9expression in stages Ⅰ (41.18%),11(70.00%),Ⅲ (82.61%),(P<0.05). The expressions of MMP-9were not related to age of onset (P>0.05) and pathological grading.VEGF expression rates of endometrial carcinoma were86.36%and62.50%in HIF-la positive group and negative group respectively, there was significant corelationship between VEGF and HIF-la (r=0.264, P=0.042). Samiliar results were obertaned in MMP-9expressions (88.64%,56.25%in HIF-la positive and negative cases respectively) and significant corelationship was found as well (r=0.358, P=0.005). The positive rates of MMP-9expressions were87.50%, and50.00%in VEGF positive and negative groups respectively, and there was a significant correlation (r=0.375, P=0.003) similar above.Conclusions:1. HIF-la, VEGF and MMP-9were over expressed in endometrial adenocarcinoma, suggesting that may be involved in the occurrence and development of endometrial carcinoma.2. Positive expressions of HIF-1α, VEGF and MMP-9in staging operation-pathology, associated with progress in endometrial adenocarcinoma.3. HIF-la, VEGF and MMP-9were positively correlated with lymph node metastasis.4. HIF-la, VEGF and MMP-9expressions were not related to pathologic grades which indicate poor prognosis with higher expressions.5.The expression of endometrial carcinoma HIF-la, VEGF and MMP-9were positively correlated, HIF-1α, MMP-9may up-regulate the expression of VEGF, and promote tumor angiogenesis, in endometrial cancer has an important role in the development, HIF-la may be regarded as a possible tumor marker in invasion and metastasis of endometrial carcinoma and a new target for tumor therapy.