血管生成素-1,-2及其受体内皮细胞特异性酪氨酸激酶受体-2表达在子宫内膜癌血管生成中的作用

Expression of Ang-1,Ang-2and Tie-2and Their Roles in Angiogenesis in Endometrial Adenocarcinoma

目的检测子宫内膜癌血管生成素(Ang)-1,Ang-2及其受体内皮细胞特异性酪氨酸激酶受体(Tie)-2的表达水平,探讨Angs/Tie-2信号途径在子宫内膜癌发生发展及血管生成中的作用。方法选择2004年5月至2012年5月广州市番禺区中心医院病理科存档的92例子宫内膜腺癌标本为研究对象,纳入子宫内膜腺癌组(n=92)。选择同期存档的54例非典型增生内膜组织标本和43例增生期子宫内膜组织标本分别纳入非典型增生内膜组(n=54)和增生期子宫内膜组(n=43)(本研究遵循的程序符合本院人体试验委员会所制定的伦理学标准,得到该委员会批准,并与之签署临床研究知情同意书)。3组被采集标本患者的年龄等一般情况比较,差异无统计学意义(P>0.05)。检测3组Ang-1,Ang-2和Tie-2阳性表达率,计算微血管密度(MVD),分析其与子宫内膜癌血管生成的关系。结果①子宫内膜腺癌组Ang-1阳性表达率显著低于非典型增生内膜组及增生期子宫内膜组,Ang-2及Tie-2阳性表达率显著高于后两者,前者分别与后两者比较,差异有统计学意义(P<0.05)。②子宫内膜腺癌组MVD值分别与非典型增生内膜组和增生期子宫内膜组比较,差异有统计学意义(P<0.05)。③子宫内膜腺癌组中Ang-1表达与MVD值呈负相关关系(P<0.05),Ang-2和Tie-2表达与MVD值均呈正相关关系(P<0.05)。④子宫内膜腺癌组FIGO分期为Ⅱ期、Ⅲ期者Ang-2和Tie-2阳性表达率较Ⅰ期显著增加,肌层浸润程度<1/2和≥1/2者Ang-2和Tie-2阳性表达率较无肌层浸润者显著增高,前两者分别同后者比较,差异均有统计学意义(P<0.05),子宫内膜癌各组织病理学分期间Ang-2和Tie-2阳性表达率比较,差异无统计学学意义(P>0.05)。结论 Ang-1,Ang-2和其受体Tie-2的表达在子宫内膜癌血管生成中具有重要作用,并且Ang-2,Tie-2表达与子宫内膜癌的FIGO分期和肌层浸润程度有关。

Objective To study the expression of angiopoietin（Ang）-1, Ang-2 and their receptor endothelium-specific receptor tyrosine kinase （Tie）-2 in endometrial adenocareinoma. Methods From May 2004 to 2012,92 cases of human primary endometrial carcinoma tissue,54 cases of atypical hyperplasia tissue and 43 cases of normal proliferative endometrium were included in the study, and divided into endometrial carcinoma group（n= 92）, atypical hyperplasia tissue group （n = 54） and normal proliferative endometrium group（n=43）. The expression of Ang-1, Ang-2 and Tie-2 were detected among three groups. MVD value was calculated among three groups as well. The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Central Hospital of Panyu. There were no significant differences in general clinical data of tissue-taken patients among three groups. Results ①The positive rate of Ang-2 and Tie-2 in endometrial carcinoma group were significantly higher than those of atypical hyperplasia tissue group and normal proliferative endometrium group,meanwhile the positive rate of Ang-1 were significantly lower than other two groups （P 〈 0. 05）. ② There had significant differences in MVD value between endometrial carcinoma group and atypical hyperplasia tissue group or normal proliferative endometrium group respectively（P〈0.05）. ③There was a positive correlation between expression of Ang-2, Tie-2 and MVD value （P〈0.05） ,however, the expression of Ang-1 was negatively correlated with MVD value （P〈0.05）. ④ The expression of Ang-2 and Tie-2 were increased as the International Federation of Gynecology and Obstetrics （FIGO） stages and myometrial invasion degrees increased （P〈0. 05）. Conclusions Ang-1, Ang-2 and Tie-2 play important roles in the angiogenesis of endometrial carcinoma, and have strong relationship with FIGO stages and myometrial invasion degrees in endometrial carcinoma.