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[血管内皮生长因子、激酶插入区受体、基质金属蛋白酶-1及转录因子Ets-1在人宫颈癌中的表达及意义]

[Expression and significance about VEGF, KDR, MMP-1, and transcription factor Ets-1 in human cervical carcinoma].

作者信息

Xu Feng-lian, Li Yu-lin, Wang Zhan-dong, Feng You-ji

机构信息

Department of Gynecology, Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, China.

出版信息

Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2003 Aug;25(4):396-400.

Abstract

OBJECTIVE

To study the expression of VEGF, KDR, MMP-1, and its transcription factor Ets-1 on the interstitial neovasculogenesis in human cervical carcinoma on molecular level, which may provide further theoretic bases on judgement of prognosis and explain interregularity between neovasculagenetic factors.

METHODS

VEGF, KDR, MMP-1, and Ets-1 were detected in 87 cervical carcinomas by in situ hybridization and immunohistochemistry. The survival curves for patients with detected tumors were compared with the curves for those without tumors. Multivariate analyses were performed with Pearson analysis.

RESULTS

VEGF mRNA and its protein were mainly expressed in cytoplasms of tumor cells, positive rate was 78.6% (68/87) and 70.4% (61/87) respectively. KDR mRNA and its protein were mainly expressed in vascular endothelial cells, as correlation coefficient between KDR and VEGF was 0.892. Over expression of MMP-1 was seen in both endothelial cells and tumor cells, especially in hyperplasia of endothelial cells. Ets-1 was mainly expressed in both endothelial cells and tumor cells, correlation coefficient between Ets-1 and KDR, MMP-1, was 0.900 and 0.873, respectively. Four factors of above were highly related with tumor differentiation, lymph nodes metastasis as well as 5 years survival rate.

CONCLUSIONS

VEGF, KDR, MMP-1, and Ets-1 are important factors on neovasculogenesis in cervical carcinoma, which may be considered to be reference indicator for determining biology behavior of cervical carcinoma, and may provide further theoretic bases on antineovasculagenetic therapy.

摘要

目的

从分子水平研究血管内皮生长因子(VEGF)、激酶插入区受体(KDR)、基质金属蛋白酶-1(MMP-1)及其转录因子Ets-1在人宫颈癌间质新生血管形成中的表达,为判断预后提供进一步的理论依据,并解释新生血管形成相关因子之间的内在规律。

方法

采用原位杂交和免疫组化方法检测87例宫颈癌组织中VEGF、KDR、MMP-1和Ets-1的表达。将检测到肿瘤的患者生存曲线与未检测到肿瘤的患者生存曲线进行比较。采用Pearson分析进行多因素分析。

结果

VEGF mRNA及其蛋白主要表达于肿瘤细胞胞质中,阳性率分别为78.6%(68/87)和70.4%(61/87)。KDR mRNA及其蛋白主要表达于血管内皮细胞,KDR与VEGF的相关系数为0.892。MMP-1在血管内皮细胞和肿瘤细胞中均有过表达,尤其在血管内皮细胞增生处。Ets-1主要表达于血管内皮细胞和肿瘤细胞,Ets-1与KDR、MMP-1的相关系数分别为0.900和0.873。上述4种因子与肿瘤分化、淋巴结转移及5年生存率密切相关。

结论

VEGF、KDR、MMP-1和Ets-1是宫颈癌新生血管形成的重要因子,可作为判断宫颈癌生物学行为的参考指标,为抗新生血管生成治疗提供进一步的理论依据。

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