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卵巢肿瘤中的血管内皮生长因子、血管内皮生长因子受体-1、血管内皮生长因子受体-2、微血管密度及内皮细胞增殖

VEGF, VEGFR-1, VEGFR-2, microvessel density and endothelial cell proliferation in tumours of the ovary.

作者信息

Orre M, Rogers P A

机构信息

Department of Obstetrics and Gynaecology, Monash University, Monash Medical Centre, Melbourne, Australia.

出版信息

Int J Cancer. 1999 Apr 20;84(2):101-8. doi: 10.1002/(sici)1097-0215(19990420)84:2<101::aid-ijc2>3.0.co;2-5.

DOI:10.1002/(sici)1097-0215(19990420)84:2<101::aid-ijc2>3.0.co;2-5
PMID:10096239
Abstract

VEGF is an angiogenic factor with potent endothelial cell (EC) proliferative actions. Our aim was to investigate whether expression of VEGF and its receptors and EC proliferation differ between ovarian tumour types and regions of the vasculature. VEGF, VEGFR-1, VEGFR-2 and EC proliferation were examined immuno-histochemically, and in situ hybridisation (ISH) studies of VEGF mRNA expression were performed and assessed in regions of high (HVD) and average (AVD) vessel density. VEGF immunostaining was significantly stronger in HVD regions of malignant compared with borderline serous tumours. VEGF immunostaining did not differ between tumour types; however, the percentage of VEGFR-1- and VEGFR-2-positive vessels was significantly lower in mucinous tumours. No differences were observed between HVD and AVD regions. VEGF ISH signal was observed in 2/7 borderline mucinous tumours, 8/14 malignant serous tumours and 5/13 benign tumours. The EC proliferation index was significantly lower in the HVD regions of serous relative to benign tumours. A negative correlation between VEGFR-1 immunostaining and microvessel density was observed in benign and serous tumours. However, EC proliferation index and VEGFR-1 positivity were positively correlated in benign tumours. Our results suggest that VEGF may play a role in the control of angiogenesis in serous and benign tumours but it does not appear to contribute to the previously reported higher microvessel density in mucinous tumours or to influence heterogeneity of microvessel density in ovarian tumours.

摘要

血管内皮生长因子(VEGF)是一种具有强大内皮细胞(EC)增殖作用的血管生成因子。我们的目的是研究VEGF及其受体的表达以及EC增殖在不同卵巢肿瘤类型和脉管系统区域之间是否存在差异。采用免疫组织化学方法检测VEGF、血管内皮生长因子受体-1(VEGFR-1)、血管内皮生长因子受体-2(VEGFR-2)以及EC增殖情况,并在高血管密度(HVD)区域和平均血管密度(AVD)区域进行VEGF mRNA表达的原位杂交(ISH)研究并进行评估。与交界性浆液性肿瘤相比,恶性肿瘤HVD区域的VEGF免疫染色明显更强。不同肿瘤类型之间VEGF免疫染色无差异;然而,黏液性肿瘤中VEGFR-1和VEGFR-2阳性血管的百分比显著更低。HVD区域和AVD区域之间未观察到差异。在2/7例交界性黏液性肿瘤、8/14例恶性浆液性肿瘤和5/13例良性肿瘤中观察到VEGF ISH信号。浆液性肿瘤HVD区域的EC增殖指数相对于良性肿瘤显著更低。在良性肿瘤和浆液性肿瘤中观察到VEGFR-1免疫染色与微血管密度呈负相关。然而,在良性肿瘤中EC增殖指数与VEGFR-1阳性呈正相关。我们的结果表明,VEGF可能在浆液性肿瘤和良性肿瘤的血管生成控制中起作用,但它似乎并未导致先前报道的黏液性肿瘤中更高的微血管密度,也未影响卵巢肿瘤微血管密度的异质性。

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