Libard Sylwia, Popova Svetlana N, Amini Rose-Marie, Kärjä Vesa, Pietiläinen Timo, Hämäläinen Kirsi M, Sundström Christer, Hesselager Göran, Bergqvist Michael, Ekman Simon, Zetterling Maria, Smits Anja, Nilsson Pelle, Pfeifer Susan, de Ståhl Teresita Diaz, Enblad Gunilla, Ponten Fredrik, Alafuzoff Irina
Department of Pathology, Uppsala University Hospital, Uppsala, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
PLoS One. 2014 Sep 30;9(9):e108861. doi: 10.1371/journal.pone.0108861. eCollection 2014.
Human cytomegalovirus (HCMV) has been indicated being a significant oncomodulator. Recent reports have suggested that an antiviral treatment alters the outcome of a glioblastoma. We analysed the performance of commercial HCMV-antibodies applying the immunohistochemical (IHC) methods on brain sample obtained from a subject with a verified HCMV infection, on samples obtained from 14 control subjects, and on a tissue microarray block containing cores of various brain tumours. Based on these trials, we selected the best performing antibody and analysed a cohort of 417 extra- and intra-axial brain tumours such as gliomas, medulloblastomas, primary diffuse large B-cell lymphomas, and meningiomas. HCMV protein pp65 immunoreactivity was observed in all types of tumours analysed, and the IHC expression did not depend on the patient's age, gender, tumour type, or grade. The labelling pattern observed in the tumours differed from the labelling pattern observed in the tissue with an active HCMV infection. The HCMV protein was expressed in up to 90% of all the tumours investigated. Our results are in accordance with previous reports regarding the HCMV protein expression in glioblastomas and medulloblastomas. In addition, the HCMV protein expression was seen in primary brain lymphomas, low-grade gliomas, and in meningiomas. Our results indicate that the HCMV protein pp65 expression is common in intra- and extra-axial brain tumours. Thus, the assessment of the HCMV expression in tumours of various origins and pathologically altered tissue in conditions such as inflammation, infection, and even degeneration should certainly be facilitated.
人巨细胞病毒(HCMV)已被证明是一种重要的肿瘤调节因子。最近的报告表明,抗病毒治疗会改变胶质母细胞瘤的预后。我们应用免疫组织化学(IHC)方法,分析了商用HCMV抗体在取自一名经证实感染HCMV的受试者的脑样本、14名对照受试者的样本以及包含各种脑肿瘤核心的组织微阵列块上的性能。基于这些试验,我们选择了性能最佳的抗体,并分析了417例轴内和轴外脑肿瘤队列,如胶质瘤、髓母细胞瘤、原发性弥漫性大B细胞淋巴瘤和脑膜瘤。在所有分析的肿瘤类型中均观察到HCMV蛋白pp65免疫反应性,且免疫组化表达不依赖于患者的年龄、性别、肿瘤类型或分级。在肿瘤中观察到的标记模式与在有活跃HCMV感染的组织中观察到的标记模式不同。在所研究的所有肿瘤中,高达90%表达了HCMV蛋白。我们的结果与先前关于胶质母细胞瘤和髓母细胞瘤中HCMV蛋白表达的报告一致。此外,在原发性脑淋巴瘤、低级别胶质瘤和脑膜瘤中也观察到了HCMV蛋白表达。我们的结果表明,HCMV蛋白pp65表达在轴内和轴外脑肿瘤中很常见。因此,在各种起源的肿瘤以及炎症、感染甚至变性等情况下的病理改变组织中评估HCMV表达肯定会更加便利。