gms | German Medical Science

50. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds)
12. Jahrestagung der Deutschen Arbeitsgemeinschaft für Epidemiologie (dae)

Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie
Deutsche Arbeitsgemeinschaft für Epidemiologie

12. bis 15.09.2005, Freiburg im Breisgau

A Role of Herpesviruses in Brain Tumor Development?

Meeting Abstract

  • Sabine Poltermann - DKFZ, Heidelberg
  • Brigitte Schlehofer - DKFZ, Heidelberg
  • Karen Steindorf - DKFZ, Heidelberg
  • Paul Schnitzler - Ruprecht-Karls-Universität, Heidelberg
  • Jürgen Wahrendorf - DKFZ, Heidelberg
  • Karsten Geletneky - Ruprecht-Karls-Universität, Heidelberg
  • Jörg R. Schlehofer - DKFZ, Heidelberg

Deutsche Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie. Deutsche Arbeitsgemeinschaft für Epidemiologie. 50. Jahrestagung der Deutschen Gesellschaft für Medizinische Informatik, Biometrie und Epidemiologie (gmds), 12. Jahrestagung der Deutschen Arbeitsgemeinschaft für Epidemiologie. Freiburg im Breisgau, 12.-15.09.2005. Düsseldorf, Köln: German Medical Science; 2005. Doc05gmds254

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Veröffentlicht: 8. September 2005

© 2005 Poltermann et al.
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Malignant gliomas are the most common primary brain tumors in humans and are generally rapidly fatal despite current therapies. The only confirmed risk factors are hereditary predisposition and a high dose of ionizing radiation. Other possible risk factors such as occupational, environmental or medical factors are discussed controversially. In addition, a role of viruses is suspected.

Herpesviruses are widespread in the human population, and implicated in the pathogenesis of several human malignancies (e.g. Kaposi’s sarcoma, Burkitt’s lymphoma, and Hodgkin’s disease). They establish latency, and reactivation may contribute to neoplasms.

Human cytomegalovirus (HCMV), a member of the family of herpesviruses, is a ubiquitous virus, which is trophic for a variety of tissues including glial cells. In 2002, Cobbs et al. [1] reported that of 27 gliomas examined all expressed multiple gene products of HCMV. In contrast, brain tissues from patients with meningioma, stroke, Alzheimer’s and other brain diseases were not infected by this virus [1]. Therefore, the authors suggested that HCMV might play an active role in glioma pathogenesis.

Furthermore, a sero-epidemiological case-control study investigated the role of several herpesviruses in gliomas. In 2001, Wrensch et al. [2] reported an inverse correlation of glioma cases with serum antibodies against varicella- zoster virus (VZV), Epstein-Barr virus (EBV) and herpes simplex virus (HSV). HCMV antibodies were slightly more frequently observed in glioma cases than in population controls.

The present study was conducted to evaluate the role of previous herpesvirus infections in brain tumor development by (i) assessing the prevalence of HCMV gene products and/or nucleic acids in primary brain tumor tissues and corresponding blood samples, and also (ii) analyzing the sero-prevalence of anti-HCMV, anti-VZV, anti-EBV and anti-HSV antibodies (IgM and IgG) in patients with primary brain tumors.

Material and Methods

Between December 2002 and March 2004, 95 patients with primary brain tumors (gliomas, meningiomas, acoustic neurinomas, and medulloblastomas) were included in the study. There was no age restriction for participating in the study. Overall, patients had a median age of 53 years with a range from 9 to 83 years. Biopsies from tumor tissues and blood samples of the patients were collected at the Department of Neurosurgery, University of Heidelberg.

Tumor tissues and blood samples were analyzed by nested PCR for the presence of HCMV DNA (sequences of the gB, pp65, IE1-72 genes). In addition, tumor tissues were fixed in formalin, and paraffin sections were analyzed by immunohistochemistry to detect HCMV-specific proteins (e.g. pp65, IE, EA, LA). Furthermore, patients’ sera were tested by ELISA for IgG and IgM antibodies to HCMV, VZV, EBV, and HSV, and compared to published prevalences in the German population. Prevalences and corresponding 95% confidence intervals (CI) were computed using the PROC FREQ procedure of the statistical software package SAS.


Using various PCR protocols, HCMV DNA was not detected, neither in the brain tumor tissues nor in the corresponding blood samples.

Similarly, immunohistochemistry did not reveal any of the addressed HCMV-specific proteins.

In the serological analyses of the corresponding blood samples of the patients, all sera were negative for IgM antibodies against all herpesviruses tested.

IgG seroprevalences did not differ from published reference data available for the German population. Anti-herpesvirus antibody prevalences were as follows (brain tumor cases vs. references): HCMV, 64% vs. 40-80% [3]; HSV, 84% vs. 85% [4]; VZV, 95% vs. >86% [5], [6]; EBV, 91% vs. 90% [7]. Focusing on the seroprevalences for glioma patients only, HSV antibody frequency was elevated (91%) whereas prevalences for HCMV, VZV and EBV antibodies were as for the general population.


In contrast to the study of Cobbs et al. [1], who found all of 27 gliomas positive for HCMV molecules, no HCMV genes or proteins were detected in 95 primary brain tumor tissues analyzed in the present study. It is not clear if the conflicting results are due to geographical differences in the prevalence of HCMV (USA vs. Germany). However, a very recent US study by Lau et al. in 2004 [8] also failed to detect HCMV molecules in 22 gliomas investigated, also when using the same protocols as Cobbs et al. [1]. Furthermore, serological analyses did not reveal differences in the overall sero-prevalences of antibodies to HCMV, HSV, EBV or VZV in the patients compared to the published prevalences [3], [4], [5], [6], [7]. Our data for glioma do not confirm the reduced HSV and VZV sero-prevalence of the case-control study of Wrensch et al. [2].

In summary, the present study, which is so far the largest on the prevalence of HCMV molecules in brain tumor tissues, could not confirm the hypothesis of Cobbs et al. [1] that HCMV may play a role in glioma pathogenesis. Seroprevalences in the present study indicate a possible role of HSV in glioma etiology; however, due to the small study size, these findings could also be due to chance and need to be further analyzed.


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Wrensch M, Weinberg A, Wiencke J, Miike R, Barger G, Kelsey K. Prevalence of antibodies to four herpesviruses among adults with glioma and controls. Am J Epidemiol 2001; 154(2):161-165
Humanes Cytomegalievirus (HCMV); Stellungnahmen des Arbeitskreises Blut des Bundesministeriums für Gesundheit. Bundesgesundheitsblatt 2000; 70, 653-659. Springer-Verlag
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