VEGFA表达水平及微血管密度与超选择性颅内动脉灌注贝伐珠单抗治疗复发性胶质母细胞瘤疗效的关系探讨  

The relationship between VEGF-A expression,microvessel density and the clinical efficacy of super-selective intraarterial cerebral infusion of bevacizumab in recurrent glioblastoma patients

作　　者：张顶顶 李劲松 刘涛[1] 庄宗 凌海平 张玉华 戴嵬 陶震楠 杭春华 Zhang Dingding;Li Jinsong;Liu Tao;Zhuang Zong;Ling Haiping;Zhang Yuhua;Dai Wei;Tao Zhennan;Hang Chunhua(Department of Neurosurgery,Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School,Nanjing 210008,China)

机构地区：[1]南京大学医学院附属鼓楼医院神经外科,南京210008

出　　处：《中华神经外科杂志》2024年第9期911-916,共6页Chinese Journal of Neurosurgery

基　　金：江苏省自然科学基金(SBK2022043509);南京鼓楼医院临床研究专项(2022-LCYJ-MS-37,2022-LCYJ-MS-34);南京鼓楼医院2023年度医疗新技术发展立项项目(XJSFZLX202324)。

摘　　要：目的初步探讨血管内皮生长因子A(VEGFA)、血管内皮生长因子受体(VEGFR 1)和VEGFR 2蛋白的表达情况以及肿瘤微血管密度与超选择性颅内动脉灌注贝伐珠单抗治疗复发性胶质母细胞瘤临床疗效的关系。方法回顾性纳入2017年10月至2023年5月在南京大学医学院附属鼓楼医院神经外科接受超选择性颅内动脉灌注贝伐珠单抗治疗的14例复发性胶质母细胞瘤患者,采用神经肿瘤学反应评估标准评估治疗的有效性,将获得疾病控制(包括完全缓解、部分缓解、疾病稳定)者定义为治疗有效组,未达到疾病控制者为治疗无效组,各7例。采用免疫组织化学染色法检测肿瘤组织中VEGFA、VEGFR 1/2蛋白的表达量,利用CD34免疫组织化学染色分析肿瘤内微血管密度,比较两组间VEGFA、VEGFR 1/2蛋白表达量及微血管密度的差异。结果与贝伐珠单抗治疗无效组相比,贝伐珠单抗治疗有效组患者肿瘤组织中VEGFA的表达量(分别为5.71±2.21和1.86±0.90,t=4.27,P=0.003)及微血管密度[分别为(46.7±16.7)个/400倍镜和(23.4±5.7)个/400倍镜,t=3.50,P=0.009]均明显增加,而VEGFR 1和VEGFR 2的表达量的组间差异均无统计学意义(均P>0.05)。结论初步研究表明,肿瘤组织中VEGFA的表达量和微血管密度与超选择性颅内动脉灌注贝伐珠单抗治疗复发性胶质母细胞瘤的临床疗效有关。Objective To preliminarily investigate the relationship between the expression of VEGFA,VEGFR1/2 and microvascular density in tumor tissues and the recurrent glioblastoma patients′therapeutic response to super-selective intraarterial bevacizumab.Methods Between October 2017 and May 2023,14 recurrent glioblastoma patients who received super-selective intracranial arterial infusion of bevacizumab in the Department of Neurosurgery at Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School were enrolled in this study.The efficacy of the treatment was evaluated using the Response Assessment in Neuro-Oncology(RANO)criteria.Patients who achieved disease control including complete response,partial response,stable disease were defined as the treatment-effective group,while those who did not achieve disease control were classified as the treatment-ineffective group.There were 7 patients both in the treatment-ineffective and effective group.VEGFA and VEGFR1/2 expressions were assessed by immunohistochemistry staining.Microvessel density was assessed by immunohistochemistry analysis with antibody targeting CD34.The differences in VEGFA,VEGFR 1/2 protein expression levels and microvessel density between the two groups were analyzed.Results Compared with the treatment-ineffective group,the expression level of VEGFA(5.71±2.21 vs.1.86±0.90,t=4.27,P=0.003)and microvessel density(46.7±16.7 vs.23.4±5.7 per 400×magnification,t=3.50,P=0.009)in tumor tissues significantly increased in the treatment-effective group,while there was no significant difference in the VEGFR 1/2 expression(both P>0.05).Conclusion The preliminary study has shown that expression level of VEGFA and microvessel density in tumor tissue are correlated with the clinical efficacy in recurrent glioblastoma patients treatment with super-selective intracranial arterial infusion of bevacizumab.

关 键 词：胶质母细胞瘤 复发 贝伐单抗 颅内动脉超选择灌注 血管内皮生长因子A 微血管密度 

分 类 号：R739.41[医药卫生—肿瘤]