Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma
Sensitive detection of human cytomegalovirus in tumors and peripheral blood of patients diagnosed with glioblastoma
复制标题
DOI：
10.1215/15228517-2007-035
复制
发表时间：
2008-02-01
期刊：
影响因子：
15.9
通讯作者：
Sampson, John H.
中科院分区：
文献类型：
--
作者：
Mitchell, Duane A.;Xie, Weihua;Sampson, John H.
人巨细胞病毒（HCMV）已被描述为与几种人类恶性肿瘤，虽然检测的频率仍然存在争议。目前尚不清楚HCMV是否在恶性肿瘤进展中起积极作用，或在导致慢性炎症或免疫抑制的病理条件下重新激活。在这项研究中，我们报告的调查检测HCMV在肿瘤和外周血中的新诊断的多形性胶质母细胞瘤（GBM）患者。采用免疫组织化学，原位杂交，和聚合酶链反应扩增病毒DNA，HCMV的检测进行了研究，从GBM患者的肿瘤和血液标本，以及在正常志愿者和接受开颅手术的诊断GBM以外的患者的外周血。我们发现，高百分比（> 90%）的GBM肿瘤，而不是周围的正常脑，与HCMV核酸和蛋白质。此外，新诊断的GBM患者中有很大比例（80%）的外周血中可检测到HCMV DNA，而血清阳性的正常供体和其他手术患者未显示出可检测到的病毒，这表明GBM患者体内的HCMV系统性再活化或病毒DNA从感染的肿瘤细胞脱落到外周。这些结果证实了HCMV与恶性神经胶质瘤的相关性，并证明亚临床HCMV病毒血症（血液中存在病毒DNA而无感染的临床症状）是GBM患者中以前未被认识到的疾病谱。
Human cytomegalovirus (HCMV) has been described to be associated with several human malignancies, though the frequency of detection remains controversial. It is unclear whether HCMV plays an active role in malignant tumor progression or becomes reactivated under pathologic conditions that result in chronic inflammation or immunosuppression. In this study, we report on the investigation of detecting HCMV in the tumors and peripheral blood of patients with newly diagnosed glioblastoma multiforme (GBM). Using immunohistochemistry, in situ hybridization, and polymerase chain reaction amplification of viral DNA, the detection of HCMV was investigated in tumor and blood specimens from patients with GBM as well as in the peripheral blood of normal volunteers and patients undergoing craniotomy for diagnoses other than GBM. We found that a high percentage (> 90%) of GBM tumors, not surrounding normal brain, are associated with HCMV nucleic acids and proteins. Furthermore, a significant proportion of patients (80%) with newly diagnosed GBM have detectable HCMV DNA in their peripheral blood, while seropositive normal donors and other surgical patients did not exhibit detectable virus, suggesting either a systemic reactivation of HCMV within patients with GBM or shedding of viral DNA from infected tumor cells into the periphery. These results confirm the association of HCMV with malignant gliomas and demonstrate that subclinical HCMV viremia (presence of viral DNA in blood without clinical symptoms of infection) is a previously unrecognized disease spectrum in patients with GBM.