血管内皮生长因子及其受体在子宫内膜癌中的表达

[Expression of vascular endothelial growth factor and its receptors in endometrial carcinoma].

作者信息

Wang Haiyan, Chen Guian, Zhang Bo

机构信息

Department of Obstetrics and Gynecology, The Third Hospital, Peking University, Beijing 100083, China.

出版信息

Zhonghua Bing Li Xue Za Zhi. 2002 Oct;31(5):391-5.

PMID:12485477

Abstract

OBJECTIVE

To study the expression of vascular endothelial growth factor (VEGF) and its receptors, the fms-like tyrosine-1 (flt-1) and kinase insert domain-containing receptor (KDR) in endometrial carcinoma and investigate the functions of VEGF and its receptors for endometrial carcinoma angiogenesis and its relation to the grade of tumor.

METHODS

Immunocytochemistry and in situ hybridization technique were used to measure the level of VEGF, flt-1, KDR protein and mRNA in endometrial carcinoma tissue from 23 patients and endometrial samples from 6 normal menopausal women. A few endometrial carcinoma samples were homogenized for Western blot analysis. The blood vessel density was estimated by counting blood vessels stained with endothelial marker VIII factor.

RESULTS

The VEGF and its receptors were widely expressed in the cytoplasm of endothelial cells and tumor cells of endometrial carcinoma. The level of VEGF protein in endothelial cells and endometrial cancer cells of grade II and III tumor tissues was higher than that in grade I and normal menopausal endometrium (P < 0.05). VEGF mRNA did not show higher expression with the increase of tumor grade but its expression in normal tissue was lower than that in cancer (P < 0.05). The expression of flt-1 protein and mRNA in endothelial cells got higher in III than in grade II and I (P < 0.05), but invariable in cancer cells (P > 0.05), flt-1 expression in cancer was higher than that in normal menopausal endometrium either in endothelial cells or in cancer cells (P < 0.05). The expression of KDR protein in endothelial and cancer cell was high but did not alter with the increase of tumor grade (P > 0.05), the level of its mRNA was higher in cancer than that in normal tissue (P < 0.05). The microvascular density in grade III (48 +/- 12) was higher than that in grade II (26 +/- 16), grade I (27 +/- 14) and normal menopausal tissue (26 +/- 11, P < 0.05).

CONCLUSIONS

The expression pattern of VEGF, flt-1 and KDR protein and mRNA increased with the increase of tumor grade in endometrial carcinoma indicates that VEGF and its receptors contribute to the neovascularization of tumors and is one of the factors that relate to rapid tumor growth of endometrial carcinoma.

摘要

目的

研究血管内皮生长因子（VEGF）及其受体，即fms样酪氨酸激酶-1（flt-1）和含激酶插入结构域受体（KDR）在子宫内膜癌中的表达，探讨VEGF及其受体在子宫内膜癌血管生成中的作用及其与肿瘤分级的关系。

方法

采用免疫细胞化学和原位杂交技术检测23例子宫内膜癌组织及6例正常绝经后妇女子宫内膜组织中VEGF、flt-1、KDR蛋白及mRNA水平。取部分子宫内膜癌组织匀浆进行蛋白质印迹分析。通过计数内皮标志物VIII因子染色的血管来估计血管密度。

结果

VEGF及其受体在子宫内膜癌内皮细胞和肿瘤细胞的细胞质中广泛表达。II级和III级肿瘤组织的内皮细胞和子宫内膜癌细胞中VEGF蛋白水平高于I级和正常绝经后子宫内膜（P<0.05）。VEGF mRNA未随肿瘤分级增加而表现出更高表达，但其在正常组织中的表达低于癌组织（P<0.05）。III级内皮细胞中flt-1蛋白和mRNA表达高于II级和I级（P<0.05），但在癌细胞中无变化（P>0.05），癌组织中flt-1在内皮细胞和癌细胞中的表达均高于正常绝经后子宫内膜（P<0.05）。KDR蛋白在内皮细胞和癌细胞中表达较高，但不随肿瘤分级增加而改变（P>0.05），其mRNA水平在癌组织中高于正常组织（P<0.05）。III级微血管密度（48±12）高于II级（26±16）、I级（27±14）和正常绝经后组织（26±11，P<0.05）。