Influence of VEGF-A, VEGFR-1-3, and neuropilin 1-2 on progression-free: and overall survival in WHO grade II and III meningioma patients.
Influence of VEGF-A, VEGFR-1-3, and neuropilin 1-2 on progression-free: and overall survival in WHO grade II and III meningioma patients.
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DOI：
10.1007/s10735-020-09940-2
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发表时间：
2021-04
影响因子：
3.2
通讯作者：
Baumgarten P
中科院分区：
文献类型：
--
作者：
Bernatz S;Monden D;Gessler F;Radic T;Hattingen E;Senft C;Seifert V;Ronellenfitsch MW;Plate KH;Harter PN;Baumgarten P
较高级别的脑膜瘤往往会复发。我们的目的是评估 WHO II 级和 III 级脑膜瘤中血管内皮生长因子 (VEGF)-A 与 VEGF 受体 1-3 以及辅助受体 Neuropilin (NRP)-1 和 -2 的蛋白水平，以阐明靶向治疗的基本原理。我们调查了 147 名颅脑膜瘤患者的 232 份标本，其中包括复发性肿瘤。在组织微阵列上进行 VEGF-A、VEGFR-1-3 和 NRP-1/-2 的免疫组织化学分析。我们应用了半定量评分（染色强度 x 频率）。 VEGF-A、VEGFR-1-3 和 NRP-1 表达异质。 NRP-2主要不存在。我们证明 WHO III 级脑膜瘤中肿瘤细胞的 VEGF-A 水平显着增加 (p = 0.0098)。我们发现肿瘤细胞和血管上 VEGF-A 和 VEGFR-1 的表达水平呈正相关 (p < 0.0001)。此外，肿瘤血管上 VEGF-A 和 VEGFR-3 表达呈正相关（p = 0.0034）。 VEGFR-2 表达与无进展生存期呈正相关 (p = 0.0340)。肿瘤细胞上的 VEGF-A 与总生存率呈负相关 (p = 0.0084)。 VEGF-A 驱动的肿瘤血管生成系统可能仍然是恶性脑膜瘤疾病辅助治疗的合适靶点。然而，它在恶性肿瘤进展中的作用可能并不像预期的那么重要。在进行抗血管生成治疗之前对配体和所有受体进行全面测试的价值需要在临床试验中进行评估。
Higher grade meningiomas tend to recur. We aimed to evaluate protein levels of vascular endothelial growth factor (VEGF)-A with the VEGF-receptors 1-3 and the co-receptors Neuropilin (NRP)-1 and -2 in WHO grade II and III meningiomas to elucidate the rationale for targeted treatments. We investigated 232 specimens of 147 patients suffering from cranial meningioma, including recurrent tumors. Immunohistochemistry for VEGF-A, VEGFR-1-3, and NRP-1/-2 was performed on tissue micro arrays. We applied a semiquantitative score (staining intensity x frequency). VEGF-A, VEGFR-1-3, and NRP-1 were heterogeneously expressed. NRP-2 was mainly absent. We demonstrated a significant increase of VEGF-A levels on tumor cells in WHO grade III meningiomas (p = 0.0098). We found a positive correlation between expression levels of VEGF-A and VEGFR-1 on tumor cells and vessels (p < 0.0001). In addition, there was a positive correlation of VEGF-A and VEGFR-3 expression on tumor vessels (p = 0.0034). VEGFR-2 expression was positively associated with progression-free survival (p = 0.0340). VEGF-A on tumor cells was negatively correlated with overall survival (p = 0.0084). The VEGF-A-driven system of tumor angiogenesis might still present a suitable target for adjuvant therapy in malignant meningioma disease. However, its role in malignant tumor progression may not be as crucial as expected. The value of comprehensive testing of the ligand and all receptors prior to administration of anti-angiogenic therapy needs to be evaluated in clinical trials.
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