目的:阐明松弛素在成人和儿童脑海绵状畸形(CCMs)中的作用,作者研究了松弛素1、2和3的内皮细胞(EC)表达;血管内皮生长因子受体-1和-2(VEGFR-1和-2);Ki-67;血管几何形状;和出血,以及32例手术切除病变患者的临床表现。
方法:用松弛素1、2和3的抗体对32例CCM和5例正常非血管病变对照(NVLC)脑组织样本的石蜡包埋切片进行免疫组织化学染色;血管生成生长因子受体Flt-1(VEGFR-1)和Flk-1(VEGFR-2);和增殖标记Ki-67。对于形态测量分析,使用ElasticavanGieson染色剂,为了证明出血,使用了特恩布尔染色。将儿科和成人CCM的数据相互比较,并与从NVLC获得的数据进行比较。用Fisher精确检验进行统计分析,卡方检验,PHI相关系数,和学生t检验。P值<0.05被认为是显著的。
结果:儿童和成人海绵体瘤血管直径没有显著差异。在CCM中观察到出血,但在NVLC样品中未观察到出血(p<0.05)。Ki-67、VEGFR-1和-2、松弛素1、2和3在儿童和成人CCM的ECs中的表达无差异。而CCM,与对照脑组织样本相比,更频繁地表达Flt-1和松弛素2(p<0.05)。Ki-67在NVLC中没有表达,但差异无统计学意义。松弛素1和2的表达以及VEGFR-1的表达增加与幕上相对于幕下位置相关(p<0.05)。
结论:松弛素1和2以及VEGFR-1在幕上海绵状瘤中发挥作用。松弛素3可能在正常的脑血管系统中起生理作用。松弛素1和3也存在于正常的脑血管系统中。松弛素1、2和3与VEGFR-1表达增加相关。
To shed light on the role of relaxin in cerebral cavernous malformations (CCMs) in adults and children, the authors investigated endothelial cell (EC) expression of relaxin 1, 2, and 3; vascular endothelial growth factor receptor-1 and -2 (VEGFR-1 and -2); Ki-67; vascular geometry; and hemorrhage, as well as the clinical presentation of 32 patients with surgically resected lesions.
Paraffin-embedded sections of 32 CCMs and 5 normal nonvascular lesion control (NVLC) brain tissue samples were immunohistochemically stained with antibodies to relaxin 1, 2, and 3; angiogenesis growth factor receptors Flt-1 (VEGFR-1) and Flk-1 (VEGFR-2); and proliferation marker Ki-67. For morphometric analysis, Elastica van Gieson stain was used, and for hemorrhage demonstration, Turnbull stain was used. Data from the pediatric and adult CCMs were compared with each other and with those obtained from the NVLCs. Statistical analyses were performed with Fisher\'s exact test, the chi-square test, the phi correlation coefficient, and the Student t-test. A p value < 0.05 was considered significant.
Pediatric and adult cavernoma vessels did not significantly differ in diameter. Hemorrhage was observed in CCMs but not in NVLC samples (p < 0.05). There was no difference in expression of Ki-67, VEGFR-1 and -2, and relaxin 1, 2, and 3 in the ECs of pediatric and adult CCMs. The ECs of CCMs were largely negative for relaxin 3 compared to NVLCs (p < 0.05), whereas CCMs, compared to control brain tissue samples, more frequently expressed Flt-1 and relaxin 2 (p < 0.05). Ki-67 was not expressed in the NVLCs, but the difference was not statistically significant. Relaxin 1 and 2 expression and increased expression of VEGFR-1 were associated with a supra- versus infratentorial location (p < 0.05).
Relaxin 1 and 2 and VEGFR-1 play a role in supratentorial cavernomas. Relaxin 3 may play a physiological role in normal brain vasculature. Relaxin 1 and 3 are also found in normal cerebral vasculature. Relaxin 1, 2, and 3 are associated with increased VEGFR-1 expression.