血管内皮生长因子A、血管内皮生长因子受体2、血管内皮生长因子受体3及相关蛋白在子宫内膜癌中的表达谱分析及其意义

Expression profiling and significance of VEGF-A, VEGFR2, VEGFR3 and related proteins in endometrial carcinoma.

作者信息

Wang Jayson, Taylor Alexandra, Showeil Rania, Trivedi Pritesh, Horimoto Yoshiya, Bagwan Izhar, Ewington Lauren, Lam Eric W-F, El-Bahrawy Mona A

机构信息

Department of Histopathology, Imperial College London, UK.

Department of Gynaecology, Royal Marsden Hospital, UK.

出版信息

Cytokine. 2014 Aug;68(2):94-100. doi: 10.1016/j.cyto.2014.04.005. Epub 2014 May 4.

DOI:10.1016/j.cyto.2014.04.005

PMID:24845798

Abstract

BACKGROUND

Angiogenesis plays a key role in the progression of various tumors, including endometrial carcinomas. Several cytokines and their associated receptors are shown to be involved, particularly VEGF-A with VEGFR1, -2 and -3.

METHODS

The expressions of VEGF-A, VEGFR2 and VEGFR3 were studied in by immunohistochemistry in 76 endometrial carcinoma specimens. VEGFR2 and VEGFR3 receptor expression were also studied by qRT-PCR in 17 tumors in comparison to normal endometrium. The expression profiles were correlated with tumor type, grade, stage, lymphovascular invasion, disease free survival, and the expressions of other cytokine receptors (EGFR, CXCR1 and CXCR2).

RESULTS

Immunohistochemically, 63% of endometrial cancers expressed VEGF-A, 55% VEGFR2 and 26% VEGFR3. VEGFR3 was significantly correlated with tumor stage (p=0.02), with a trend towards poorer disease free survival (p=0.09). VEGF-A was significantly correlated with microvessel density (p<0.01). Using qRT-PCR, increased expression of VEGFR2 (17.2-fold) and VEGFR3 (21.9-fold) was seen in endometrial carcinomas compared with normal endometrium, with significant correlations among the expression levels of VEGFR2, VEGFR3, EGFR, CXCR1 and CXCR2.

CONCLUSION

Our study suggests that evaluation of VEGFR3 expression in tumors may provide prognostic data, and help identify patients who would best benefit from anti-angiogenic therapeutic agents. This is the first report showing correlations between the expressions levels of the different receptors.

摘要

背景

血管生成在包括子宫内膜癌在内的各种肿瘤进展中起关键作用。已表明几种细胞因子及其相关受体参与其中，特别是血管内皮生长因子A（VEGF-A）与血管内皮生长因子受体1（VEGFR1）、-2和-3。

方法

采用免疫组织化学方法研究了76例子宫内膜癌标本中VEGF-A、VEGFR2和VEGFR3的表达。还通过定量逆转录聚合酶链反应（qRT-PCR）研究了17例肿瘤与正常子宫内膜中VEGFR2和VEGFR3受体的表达。将表达谱与肿瘤类型、分级、分期、淋巴管浸润、无病生存期以及其他细胞因子受体（表皮生长因子受体（EGFR）、CXC趋化因子受体1（CXCR1）和CXC趋化因子受体2（CXCR2））的表达进行关联分析。

结果

免疫组织化学结果显示，63%的子宫内膜癌表达VEGF-A，55%表达VEGFR2，26%表达VEGFR3。VEGFR3与肿瘤分期显著相关（p=0.02），无病生存期有较差趋势（p=0.09）。VEGF-A与微血管密度显著相关（p<0.01）。通过qRT-PCR发现，与正常子宫内膜相比，子宫内膜癌中VEGFR2（17.2倍）和VEGFR3（21.9倍）表达增加，VEGFR2、VEGFR3、EGFR、CXCR1和CXCR2的表达水平之间存在显著相关性。