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Abstract：
It is acknowledged that conventional renal cell carcinoma (cRCC), which makes up 85% of renal malignancies, is a highly vascular tumor. Humanized monoclonal antibodies were developed to inhibit tumor neo-angiogenesis, which is driven by VEGFA/KDR signaling. The results largely met our expectations, and in several cases, adverse events occurred. Our study aimed to analyze the expression of VEGFA and its receptor KDR by immunohistochemistry in tissue multi-array containing 811 cRCC and find a correlation between VEGFA/KDR signaling and new vessel formation. None of the 811 cRCC displayed VEGFA-positive immunostaining. However, each glomerulus in normal kidney showed VEGFA-positive endothelial cells. KDR expression in endothelial meshwork was found in only 9% of cRCC, whereas 2% of the cRCC displayed positive KDR reaction in the cytoplasm of tumor cells. Our results disclose the involvement of VEGFA/KDR signaling in the neo-vascularization of cRCC and explain the frequent resistance to drugs targeting the VEGFA/KDR signaling and the high frequency of adverse events.
摘要：
众所周知，常规肾细胞癌(cRCC)，占肾脏恶性肿瘤的85%，是高度血管性肿瘤.开发了人源化单克隆抗体来抑制肿瘤新血管生成，由VEGFA/KDR信号驱动。结果基本上符合我们的预期，在一些情况下，不良事件发生。我们的研究旨在通过免疫组织化学方法分析含有811cRCC的组织多阵列中VEGFA及其受体KDR的表达，并发现VEGFA/KDR信号传导与新血管形成之间的相关性。811cRCC均未显示VEGFA阳性免疫染色。然而,正常肾脏的每个肾小球均显示VEGFA阳性内皮细胞。仅在9%的cRCC中发现内皮网中的KDR表达，而2％的cRCC在肿瘤细胞的细胞质中显示出阳性的KDR反应。我们的结果揭示了VEGFA/KDR信号参与cRCC的新血管形成，并解释了对靶向VEGFA/KDR信号的药物的频繁耐药和不良事件的高频率。
