Article
Cytomegalovirus infection as potential factor in CNS tumor development and progression
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Published: | September 11, 2012 |
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There is increasing evidence that cytomegalovirus (CMV) infection is involved in oncogenic transformation and oncomodulation in humans. Furthermore, tumor growth and immune escape could be dampened by anti-CMV treatment in preclinical studies. Most recently, several studies stated that over 90% of tissue samples from glioblastoma patients display CMV infection while remote normal appearing tissue of the same cohort remain CMV-negative. In medulloblastomas, CMV infection has even been presented as an etiological factor for tumor development and antiviral therapy has been proposed as additional treatment approach. Since current protocols for in vivo detection of tumor-associated CMV infection are considerably different from high-throughput diagnostic methods, there is an urgent need for new diagnostic tools which allow the detection of CMV on slide in tumor samples since in tumors viral load is supposed to be much lower as compared to inflammatory CMV lesions. Therefore, we established an immunohistochemical detection set-up including positive, negative and isotype controls for pp65 and immediate early CMV antigen. We further established a cellular titration series applying various titers of CMV infection (ranging from 1:1 up to 1:256) in UKF-NB4 neuroblastoma cells. By doing so we could establish a highly sensitive, controlled detection method for CMV infection which reached similar detection limits as in corresponding PCR analyses. Until now, we screened over 100 CNS tumors for CMV infection (among others glioblastomas, medulloblastomas and brain metastases) and obtained constantly negative results in our cohort. In conclusion, our highly sensitive CMV detection set-up is still not suitable to reproduce previous findings of high CMV infection rates in CNS neoplasms, therefore high-throughput detection tools for tumor-related CMV infections still remain to be established.