Liu Zhen, Li Liang, Yi Zhiqiang, Duan Hongzhou, Lu Runchun, Li Chunwei, Zhou Jingcheng, Gong Kan
Department of Neurosurgery, Peking University First Hospital, Beijing, China.
Department of Urology, Peking University First Hospital, Beijing, China.
Front Oncol. 2020 May 5;10:703. doi: 10.3389/fonc.2020.00703. eCollection 2020.
Central nervous system (CNS) hemangioblastomas (HGBs) are the most frequent cause of mortality in patients with von Hippel-Lindau (VHL) disease. Characteristics of multiple and recurrent disease cause certain difficulties in the treatment of CNS HGBs. VHL-related HGB cases treated surgically at our hospital from September 2015 to February 2019 were analyzed. Patients meeting the clinical diagnostic criteria underwent genetic testing. Real-time PCR and immunohistochemistry were used in HGBs to verify differential expression of mRNAs and proteins, respectively. Furthermore, correlations between the differentially expressed proteins and the histological grading, genetic mutations, and tumor burden were also analyzed. A total of 21 patients with VHL syndrome confirmed by genetic testing (missense group, 9; partial deletion group, 12) were enrolled, and 30 CNS HGBs from these patients were studied. Clinical data showed that men at first operation were significantly younger than females ( = 0.005). Real-time PCR demonstrated that ( = 0.017) and α ( = 0.017) mRNA expression in VHL-related HGBs was significantly higher than that in the control group. Immunohistochemistry showed that the mean optical density in VHL-related HGBs was significantly higher than that in controls (EGFR, = 0.007; TGFα, = 0.021). Finally, the cyst volume was related to the upregulation of EGFR ( = 0.782, < 0.01). Overexpression of EGFR and TGFα may contribute to tumor growth in VHL-related CNS HGBs. The cyst volume was associated with EGFR overexpression. These results provide information for the management of VHL-related HGBs in the era of targeted therapeutics.
中枢神经系统（CNS）血管母细胞瘤（HGBs）是冯·希佩尔-林道（VHL）病患者最常见的死亡原因。多发性和复发性疾病的特征给CNS HGBs的治疗带来了一定困难。对2015年9月至2019年2月在我院接受手术治疗的VHL相关HGB病例进行了分析。符合临床诊断标准的患者接受了基因检测。在HGBs中分别使用实时荧光定量聚合酶链反应（Real-time PCR）和免疫组织化学来验证mRNA和蛋白质的差异表达。此外，还分析了差异表达蛋白与组织学分级、基因突变和肿瘤负荷之间的相关性。共纳入21例经基因检测确诊的VHL综合征患者（错义组9例；部分缺失组12例），并对这些患者的30个CNS HGBs进行了研究。临床资料显示，初次手术时男性患者明显比女性患者年轻（P = 0.005）。实时荧光定量聚合酶链反应表明，VHL相关HGBs中β（P = 0.017）和α（P = 0.017）mRNA表达明显高于对照组。免疫组织化学显示，VHL相关HGBs的平均光密度明显高于对照组（表皮生长因子受体（EGFR），P = 0.007；转化生长因子α（TGFα），P = 0.021）。最后，囊肿体积与EGFR的上调有关（r = 0.782，P < 0.01）。EGFR和TGFα的过表达可能促进VHL相关CNS HGBs的肿瘤生长。囊肿体积与EGFR过表达有关。这些结果为靶向治疗时代VHL相关HGBs的管理提供了信息。
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