Holdhoff Matthias, Guner Gunes, Rodriguez Fausto J, Hicks Jessica L, Zheng Qizhi, Forman Michael S, Ye Xiaobu, Grossman Stuart A, Meeker Alan K, Heaphy Christopher M, Eberhart Charles G, De Marzo Angelo M, Arav-Boger Ravit
Brain Cancer Program, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Oncology, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Clin Cancer Res. 2017 Jun 15;23(12):3150-3157. doi: 10.1158/1078-0432.CCR-16-1490. Epub 2016 Dec 29.
Reports of cytomegalovirus (CMV) detection in high-grade gliomas (HGG)/glioblastoma have been conflicting. We undertook a comprehensive approach to determine the presence or absence of CMV in tissue, plasma, and serum of HGG patients. In a retrospective arm, 25 fresh frozen tissues from glioblastoma patients were tested for CMV by real-time PCR. Tissue microarrays from 70 HGG patients were tested by IHC and 20 formalin-fixed paraffin-embedded (FFPE) glioblastoma tissues by IHC and chromogenic hybridization (CISH), targeting CMV-encoded IE1/2 and pp65. In a prospective arm, 18 patients with newly diagnosed HGG provided tissue and blood samples. All retrospectively collected tissues were negative for CMV by all methods. In the prospective cohort, 18 patients with newly diagnosed HGG provided blood samples at the time of diagnosis and during follow-up. Of 38 plasma specimens, CMV DNA was detected in 3 of 18 samples at baseline and 1 of 20 follow-up samples. Serum CMV IgG was positive in 8 of 15 (53%) of patients. Among the FFPE samples tested in the prospective arm, all were negative for CMV by IHC, CISH, and PCR. Utilizing 6 highly sensitive assays with three orthogonal technologies on multiple specimens and specimen types, no evidence for CMV in glioblastoma tissues was found. Our findings call for multicenter blinded analyses of samples collected from different geographical areas with agreed upon study designs and determination of causality or lack thereof of CMV in HGG/glioblastoma for future guidance on the necessary antiviral and/or CMV-based therapies. .
关于在高级别胶质瘤（HGG）/胶质母细胞瘤中检测巨细胞病毒（CMV）的报告一直存在矛盾。我们采用了一种综合方法来确定HGG患者的组织、血浆和血清中是否存在CMV。在回顾性研究中，通过实时PCR对25例胶质母细胞瘤患者的新鲜冷冻组织进行了CMV检测。对70例HGG患者的组织微阵列进行了免疫组织化学（IHC）检测，并对20例福尔马林固定石蜡包埋（FFPE）的胶质母细胞瘤组织进行了IHC和显色杂交（CISH）检测，检测靶点为CMV编码的IE1/2和pp65。在前瞻性研究中，18例新诊断的HGG患者提供了组织和血液样本。所有回顾性收集的组织通过所有方法检测CMV均为阴性。在前瞻性队列中，18例新诊断的HGG患者在诊断时和随访期间提供了血液样本。在38份血浆标本中，18份基线样本中有3份检测到CMV DNA，20份随访样本中有1份检测到。15例患者中有8例（53%）血清CMV IgG呈阳性。在前瞻性研究中检测的FFPE样本中，所有样本通过IHC、CISH和PCR检测CMV均为阴性。利用6种高度敏感的检测方法，采用三种正交技术对多个样本和样本类型进行检测，未在胶质母细胞瘤组织中发现CMV的证据。我们的研究结果呼吁采用商定的研究设计，对从不同地理区域收集的样本进行多中心盲法分析，并确定HGG/胶质母细胞瘤中CMV的因果关系或缺乏因果关系，以便为未来必要的抗病毒和/或基于CMV的治疗提供指导。
