Expression of the vascular endothelial growth factor receptor-2/Fik-1 in breast carcinomas: Correlation with proliferation
Expression of the vascular endothelial growth factor receptor-2/Fik-1 in breast carcinomas: Correlation with proliferation
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DOI：
10.1053/hupa.2002.126879
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发表时间：
2002-09-01
期刊：
影响因子：
3.3
通讯作者：
Louvrou, A
中科院分区：
文献类型：
--
作者：
Nakopoulou, L;Stefanaki, K;Louvrou, A
血管内皮生长因子（VEGF）及其受体Flk-1/KDR在血管通透性和肿瘤血管生成中起重要作用。基于VEGF/Flk-1系统可能在乳腺癌发生中起调节作用的假设，我们研究了Flk-1在141例浸润性乳腺癌中的表达与临床和免疫组化预后参数的相关性，包括增殖指数如Ki-67和拓扑异构酶Ha（Topo-Ha）。用免疫组化方法检测Flk-1、p53、Bcl-2、c-erbB-2、M-67、Topo-Ha、ER和PR。Flk-1在141例浸润性乳腺癌中的91例（64.5%）中表达，显示其在大多数肿瘤细胞中广泛表达。Flk-1表达与患者的绝经状态（P = 0.051）和浸润性乳腺癌的核分级（P = 0.003）相关，但与组织学分级、分期和患者生存率无关。有趣的是，Flk-1表达与Ki-67（P = 0.037）和topo-II α（P = 0.009）这两个公认的增殖指标显著相关，而与ER、PR、p53、Bcl-2和c-erbB-2的表达无关。此外，Flk-1表达与TIMP-1 mRNA在肿瘤内基质细胞中的定位呈负相关（P = 0.013）。总之，浸润性乳腺癌中Flk-1表达与增殖指数如Ki-67和Topo-IIa的显著相关性表明VEGF可能通过其受体Flk-1对乳腺癌细胞发挥生长因子活性。另一方面，肿瘤内基质细胞中Flk-1与TIMP-1 mRNA的负相关性支持TIMP-1可能对血管生成具有抑制作用的观点。版权所有2002，爱思唯尔科学（美国）。All rights reserved.
Vascular endothelial growth factor (VEGF) and its receptor Flk-1/KDR play an important role in vascular permeability and tumor angiogenesis. Prompted by the hypothesis that VEGF/Flk-1 system may have regulatory roles in breast carcinogenesis, we investigated the expression of Flk-1 in 141 invasive breast carcinomas in correlation with clinical and immunohistochemical prognostic parameters, including proliferation indices like Ki-67 and Topoisomerase Ha (Topo-Ha). The immunohistochemical avidin-biotin-peroxidase method was performed on paraffin sections for the detection of Flk-1, p53, Bcl-2, c-erbB-2, M-67, Topo-Ha, ER, and PR. Flk-1 was detected in 91 of 141 (64.5%) of invasive breast carcinomas showing a widespread cytoplasmic expression in most of the neoplastic cells. Flk-1 expression was correlated with the menopausal status (P = 0.051) of the patient and the nuclear grade of the invasive breast carcinoma (P = 0.003), but demonstrated no correlation with histologic grade, stage, and patient survival. It is interesting that Flk-1 expression demonstrated a significant correlation with 2 well-established proliferation indices, Ki-67 (P = 0.037) and topo-IIalpha (P = 0.009), whereas there was no correlation with the expression of ER, PR, p53, Bcl-2, and c-erbB-2. Moreover, Flk-1 expression showed an inverse correlation with TIMP-I mRNA localization in intratumoral stromal cells (P = 0.013). In conclusion, the significant correlation of Flk-1 expression in invasive breast carcinomas with proliferation indices like Ki-67 and topo-IIa suggests that VEGF may exert a growth factor activity on mammary cancer cells through its receptor Flk-1. On the other hand, the inverse correlation of Flk-1 with TIMP-1 mRNA in intratumoral stromal cells supports the notion that TIMP-1 may have an inhibitory role on angiogenesis. Copyright 2002, Elsevier Science (USA). All rights reserved.