Human Cytomegalovirus Tegument Protein pp65 Is Detected in All Intra- and Extra-Axial Brain Tumours Independent of the Tumour Type or Grade

Sylwia Libard,Göran Hesselager,Christer Sundström,Rose-Marie Amini,Michael Bergqvist,Maria Zetterling,Kirsi M Hämäläinen,Gunilla Enblad,Timo Pietiläinen,Svetlana N Popova,Anja Smits,Fredrik Ponten,Pelle Nilsson,Teresita Diaz De Ståhl,Simon Ekman,Irina Alafuzoff,Vesa Kärjä,Susan Pfeifer

doi:10.1371/journal.pone.0108861

Abstract

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.

Highlights

Human cytomegalovirus (HCMV) has been associated with tumours such as primary intracerebral tumours, neuroblastoma, colorectal cancer, prostate cancer, and non-melanoma skin carcinomas in humans [1,2,3,4,5,6]
We have assessed the expression of the HCMV protein in a large cohort of intra- and extra-axial brain tumours
We noted that the HCMV protein pp65 expression was common in brain tumours and ranged from 65 to 98 percent

Summary

Introduction

Human cytomegalovirus (HCMV) has been associated with tumours such as primary intracerebral tumours, neuroblastoma, colorectal cancer, prostate cancer, and non-melanoma skin carcinomas in humans [1,2,3,4,5,6]. Particular interest has been shown for the association between the HCMV protein expression and primary, highly malignant, non-curable brain tumours such as glioblastoma (GBM) [1,7,8]. Only a few other types of brain tumours, intra- or extra-axial have been investigated regarding the HCMV protein expression [1,8,9,10,11,12]. When the HCMV DNA was investigated in a set of GBMs, only 1 out of 80 tumour cells was shown to carry the viral DNA [14]

Methods

Results

Conclusion