The clinicopathological analysis of receptor tyrosine kinases in meningiomas: the expression of VEGFR-2 in meningioma was associated with a higher WHO grade and shorter progression-free survival
The clinicopathological analysis of receptor tyrosine kinases in meningiomas: the expression of VEGFR-2 in meningioma was associated with a higher WHO grade and shorter progression-free survival
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DOI：
10.1007/s10014-018-0332-1
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发表时间：
2019-01-01
影响因子：
3.3
通讯作者：
Nojima, Takayuki
中科院分区：
文献类型：
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作者：
Nakada, Satoko;Sasagawa, Yasuo;Nojima, Takayuki
WHO II/III级脑膜瘤经常复发，目前尚无针对脑膜瘤的既定分子靶向治疗。以前没有研究显示受体酪氨酸激酶（RTK）和脑膜瘤复发之间的关联。本研究旨在阐明RTKs与脑膜瘤临床病理特征及复发的关系。我们研究了RTKs（VEGFR-1/2/3，PDGFR-α/β和c-Kit）在74例81例脑膜瘤（WHO I级，n=64，WHO II/III级，n=17）中的免疫组化表达。免疫组化显示29例WHO I级（45%）、10例WHO II级（77%）和4例WHO III级（100%）肿瘤为VEGFR-2阳性，且VEGFR-2表达与WHO分级显著相关。在单因素分析中，以探讨与复发相关的临床病理因素，Simpson IV/V级切除，较大的肿瘤大小，高VEGFR-2表达水平，WHO II/III级，高Ki-67表达水平，和PgR的非表达被确定为显着因素。此外，VEGFR-2阳性脑膜瘤患者的无进展生存期显著缩短。在多因素分析中，WHO II/III级和部位与复发显著相关。总之，我们的研究表明，VEGFR-2抑制剂可能是复发性脑膜瘤分子治疗的最佳候选药物之一。
WHO grade II/III meningiomas recur frequently and there is currently no established molecular target therapy for meningioma. No previous studies have revealed the association between receptor tyrosine kinases (RTKs) and the recurrence of meningiomas. This study aims to elucidate the association between RTKs and the clinicopathological characteristics and recurrence of meningioma. We investigated the immunohistochemical expression of RTKs (VEGFR-1/2/3, PDGFR-alpha/beta and c-Kit) in 81 meningiomas (WHO grade I, n=64, WHO grade II/III, n=17) in 74 patients. Immunohistochemistry revealed that 29 WHO grade I (45%), 10 WHO grade II (77%), and 4 WHO grade III (100%) tumors were VEGFR-2-positive, and that the VEGFR-2 expression was significantly correlated with the WHO grade. In univariate analyses to investigate the clinicopathological factors associated with recurrence, Simpson grade IV/V resection, a larger tumor size, a high VEGFR-2 expression level, WHO grade II/III, a high Ki-67 expression level, and the non-expression of PgR were identified as significant factors. Furthermore, patients with VEGFR-2-positive meningiomas showed significantly shorter progression-free survival. In the multivariate analysis, WHO grade II/III and the location were significantly associated with recurrence. In conclusion, our study suggests that VEGFR-2 inhibitors might be one of the best candidates for molecular therapy against recurrent meningiomas.