Tumor specific VEGF-A and VEGFR2/KDR protein are co-expressed in breast cancer
Tumor specific VEGF-A and VEGFR2/KDR protein are co-expressed in breast cancer
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DOI：
10.1023/b:brea.0000004357.92232.cb
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发表时间：
2003-12-01
影响因子：
3.8
通讯作者：
Landberg, G
中科院分区：
文献类型：
--
作者：
Rydén, L;Linderholm, B;Landberg, G
血管生成是原发性乳腺癌的一个预后指标，受特异性血管生成因子及其受体的调控。血管内皮生长因子-A（VEGF-A），迄今为止被认为是最重要的，通过VEGF受体的受体酪氨酸激酶家族内的受体VEGFR 2/KDR的二聚化起作用。为了研究VEGF-A和VEGFR 2/KDR在乳腺癌中的相互作用，我们通过免疫组织化学在102例组织在肿瘤组织阵列系统中的乳腺癌中评估了它们的表达，该系统允许半定量评估胞质染色强度。此外，通过酶免疫测定（ELISA）分析从阵列中包括的102个肿瘤中的98个的冷冻组织制备的蛋白质提取物中的VEGF-A（165）。在所有样本中观察到不同强度的VEGF细胞质染色，并与VEGF含量的ELISA结果相关（p=0.007）。有趣的是，VEGFR 2/KDR表达与VEGF表达相关，使用免疫组织化学，表明VEGF和VEGFR 2/KDR可能在乳腺癌中共表达。此外，蛋白质提取物中高水平的VEGF-A（165）与受损的短期存活相关，但与长期存活无关，而化学方法评估的VEGF和VEGFR 2/KDR与存活无关。总之，使用肿瘤组织阵列系统的基于化学方法的VEGF分析似乎是一种有用的方法，用于乳腺癌中VEGF的定量，这里使用基于ELISA的方法进行了验证。肿瘤组织阵列系统使得能够同时分析参与血管生成的标记物，从而证明使用更大系列的肿瘤进行进一步研究是合理的。
Angiogenesis is a prognostic indicator in primary breast cancer regulated by specific angiogenic factors and their receptors. Vascular endothelial growth factor-A (VEGF-A), so far considered the most important, acts through dimerization of the receptor VEGFR2/KDR within the receptor tyrosine kinase family of VEGF receptors. In order to study the interplay between VEGF-A and VEGFR2/KDR in breast cancer we evaluated their expression by immunohistochemistry in 102 breast cancers organized in a tumor tissue array system allowing semi-quantitative evaluation of cytoplasmatic staining intensity. In addition, VEGF-A(165) was analyzed by an enzyme immuno assay (ELISA) in protein extracts prepared from frozen tissue from 98 of 102 tumors included in the array. Cytoplasmatic staining of VEGF of varying intensity was observed in all samples and correlated with the ELISA results of VEGF content (p=0.007). Interestingly, VEGFR2/KDR expression correlated with VEGF expression using immunohistochemistry, indicating that VEGF and VEGFR2/KDR may be co-expressed in breast cancer. Furthermore, high levels of VEGF-A(165) in the protein extracts was associated with impaired short time survival but not long term survival whereas immunohistochemically assessed VEGF and VEGFR2/KDR were not significantly associated with survival. In summary, immunohistochemically based analysis of VEGF using a tumor tissue array system seems to be a useful method for VEGF quantification in breast cancer here validated using an ELISA based method. The tumor tissue array system enables opportunities of simultaneous analysis of markers engaged in angiogenesis justifying further studies using larger series of tumors.