title: Human cytomegalovirus infection in tumor cells of the nervous system is not detectable with standardized pathologico-virological diagnostics.
abstract: BACKGROUND
  Experimental findings have suggested that human cytomegalovirus (HCMV) infection of tumor cells may exert oncomodulatory effects that enhance tumor malignancy. However, controversial findings have been published on the presence of HCMV in malignant tumors. Here, we present the first study that systematically investigates HCMV infection in human nervous system tumors by highly sensitive immunohistochemistry in correlation with the HCMV serostatus of the patients.
  
  
  METHODS
  Immunohistochemical and quantitative PCR-based methods to detect different HCMV antigens and genomic HCMV DNA were optimized prior to the investigation of pathological samples. Moreover, the pathological results were matched with the HCMV serostatus of the patients.
  
  
  RESULTS
  HCMV immediate-early, late, and pp65 antigens could be detected in single cells from HCMV strain Hi91-infected UKF-NB-4 neuroblastoma cells after 1:1024 dilution with noninfected UKF-NB-4 cells. Genomic HCMV DNA could be detected in copy numbers as low as 430 copies/mL. However, we did not detect HCMV in tumors from a cohort of 123 glioblastoma, medulloblastoma, or neuroblastoma patients. Notably, we detected nonspecifically positive staining in tumor tissues of HCMV seropositive and seronegative glioblastoma patients. The HCMV serostatus of 67 glioblastoma patients matched the general epidemiological prevalence data for Western countries (72% of female and 57% of male glioblastoma patients were HCMV seropositive). Median survival was not significantly different in HCMV seropositive versus seronegative glioblastoma patients.
  
  
  CONCLUSIONS
  The prevalence of HCMV-infected tumor cells may be much lower than previously reported based on highly sensitive detection methods.
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany (P.B., T.S., L.J., A.K.B., Mi.M.); Institute of Medical Virology, Goethe University, Frankfurt am Main, Germany (Ma.M., F.R., H.F.R., A.B., R.A., J.C.); German Cancer Consortium, Heidelberg, Germany (J.P.S., Mi.M.); German Cancer Research Center, Heidelberg, Germany (J.P.S., Mi.M.); Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany (K.F., V.S.); Senckenberg Institute of Neurooncology, University of Frankfurt am Main, Germany (K.F., J.P.S.).
authors.forename: Peter
authors.initials: P
authors.lastname: Baumgarten
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany (P.B., T.S., L.J., A.K.B., Mi.M.); Institute of Medical Virology, Goethe University, Frankfurt am Main, Germany (Ma.M., F.R., H.F.R., A.B., R.A., J.C.); German Cancer Consortium, Heidelberg, Germany (J.P.S., Mi.M.); German Cancer Research Center, Heidelberg, Germany (J.P.S., Mi.M.); Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany (K.F., V.S.); Senckenberg Institute of Neurooncology, University of Frankfurt am Main, Germany (K.F., J.P.S.).
authors.forename: Martin
authors.initials: M
authors.lastname: Michaelis
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany (P.B., T.S., L.J., A.K.B., Mi.M.); Institute of Medical Virology, Goethe University, Frankfurt am Main, Germany (Ma.M., F.R., H.F.R., A.B., R.A., J.C.); German Cancer Consortium, Heidelberg, Germany (J.P.S., Mi.M.); German Cancer Research Center, Heidelberg, Germany (J.P.S., Mi.M.); Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany (K.F., V.S.); Senckenberg Institute of Neurooncology, University of Frankfurt am Main, Germany (K.F., J.P.S.).
authors.forename: Florian
authors.initials: F
authors.lastname: Rothweiler
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany (P.B., T.S., L.J., A.K.B., Mi.M.); Institute of Medical Virology, Goethe University, Frankfurt am Main, Germany (Ma.M., F.R., H.F.R., A.B., R.A., J.C.); German Cancer Consortium, Heidelberg, Germany (J.P.S., Mi.M.); German Cancer Research Center, Heidelberg, Germany (J.P.S., Mi.M.); Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany (K.F., V.S.); Senckenberg Institute of Neurooncology, University of Frankfurt am Main, Germany (K.F., J.P.S.).
authors.forename: Tatjana
authors.initials: T
authors.lastname: Starzetz
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany (P.B., T.S., L.J., A.K.B., Mi.M.); Institute of Medical Virology, Goethe University, Frankfurt am Main, Germany (Ma.M., F.R., H.F.R., A.B., R.A., J.C.); German Cancer Consortium, Heidelberg, Germany (J.P.S., Mi.M.); German Cancer Research Center, Heidelberg, Germany (J.P.S., Mi.M.); Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany (K.F., V.S.); Senckenberg Institute of Neurooncology, University of Frankfurt am Main, Germany (K.F., J.P.S.).
authors.forename: Holger F
authors.initials: HF
authors.lastname: Rabenau
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany (P.B., T.S., L.J., A.K.B., Mi.M.); Institute of Medical Virology, Goethe University, Frankfurt am Main, Germany (Ma.M., F.R., H.F.R., A.B., R.A., J.C.); German Cancer Consortium, Heidelberg, Germany (J.P.S., Mi.M.); German Cancer Research Center, Heidelberg, Germany (J.P.S., Mi.M.); Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany (K.F., V.S.); Senckenberg Institute of Neurooncology, University of Frankfurt am Main, Germany (K.F., J.P.S.).
authors.forename: Annemarie
authors.initials: A
authors.lastname: Berger
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany (P.B., T.S., L.J., A.K.B., Mi.M.); Institute of Medical Virology, Goethe University, Frankfurt am Main, Germany (Ma.M., F.R., H.F.R., A.B., R.A., J.C.); German Cancer Consortium, Heidelberg, Germany (J.P.S., Mi.M.); German Cancer Research Center, Heidelberg, Germany (J.P.S., Mi.M.); Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany (K.F., V.S.); Senckenberg Institute of Neurooncology, University of Frankfurt am Main, Germany (K.F., J.P.S.).
authors.forename: Lukas
authors.initials: L
authors.lastname: Jennewein
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany (P.B., T.S., L.J., A.K.B., Mi.M.); Institute of Medical Virology, Goethe University, Frankfurt am Main, Germany (Ma.M., F.R., H.F.R., A.B., R.A., J.C.); German Cancer Consortium, Heidelberg, Germany (J.P.S., Mi.M.); German Cancer Research Center, Heidelberg, Germany (J.P.S., Mi.M.); Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany (K.F., V.S.); Senckenberg Institute of Neurooncology, University of Frankfurt am Main, Germany (K.F., J.P.S.).
authors.forename: Anne K
authors.initials: AK
authors.lastname: Braczynski
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany (P.B., T.S., L.J., A.K.B., Mi.M.); Institute of Medical Virology, Goethe University, Frankfurt am Main, Germany (Ma.M., F.R., H.F.R., A.B., R.A., J.C.); German Cancer Consortium, Heidelberg, Germany (J.P.S., Mi.M.); German Cancer Research Center, Heidelberg, Germany (J.P.S., Mi.M.); Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany (K.F., V.S.); Senckenberg Institute of Neurooncology, University of Frankfurt am Main, Germany (K.F., J.P.S.).
authors.forename: Kea
authors.initials: K
authors.lastname: Franz
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany (P.B., T.S., L.J., A.K.B., Mi.M.); Institute of Medical Virology, Goethe University, Frankfurt am Main, Germany (Ma.M., F.R., H.F.R., A.B., R.A., J.C.); German Cancer Consortium, Heidelberg, Germany (J.P.S., Mi.M.); German Cancer Research Center, Heidelberg, Germany (J.P.S., Mi.M.); Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany (K.F., V.S.); Senckenberg Institute of Neurooncology, University of Frankfurt am Main, Germany (K.F., J.P.S.).
authors.forename: Volker
authors.initials: V
authors.lastname: Seifert
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany (P.B., T.S., L.J., A.K.B., Mi.M.); Institute of Medical Virology, Goethe University, Frankfurt am Main, Germany (Ma.M., F.R., H.F.R., A.B., R.A., J.C.); German Cancer Consortium, Heidelberg, Germany (J.P.S., Mi.M.); German Cancer Research Center, Heidelberg, Germany (J.P.S., Mi.M.); Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany (K.F., V.S.); Senckenberg Institute of Neurooncology, University of Frankfurt am Main, Germany (K.F., J.P.S.).
authors.forename: Joachim P
authors.initials: JP
authors.lastname: Steinbach
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany (P.B., T.S., L.J., A.K.B., Mi.M.); Institute of Medical Virology, Goethe University, Frankfurt am Main, Germany (Ma.M., F.R., H.F.R., A.B., R.A., J.C.); German Cancer Consortium, Heidelberg, Germany (J.P.S., Mi.M.); German Cancer Research Center, Heidelberg, Germany (J.P.S., Mi.M.); Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany (K.F., V.S.); Senckenberg Institute of Neurooncology, University of Frankfurt am Main, Germany (K.F., J.P.S.).
authors.forename: Regina
authors.initials: R
authors.lastname: Allwinn
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany (P.B., T.S., L.J., A.K.B., Mi.M.); Institute of Medical Virology, Goethe University, Frankfurt am Main, Germany (Ma.M., F.R., H.F.R., A.B., R.A., J.C.); German Cancer Consortium, Heidelberg, Germany (J.P.S., Mi.M.); German Cancer Research Center, Heidelberg, Germany (J.P.S., Mi.M.); Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany (K.F., V.S.); Senckenberg Institute of Neurooncology, University of Frankfurt am Main, Germany (K.F., J.P.S.).
authors.forename: Michel
authors.initials: M
authors.lastname: Mittelbronn
authors.affiliation: Neurological Institute (Edinger Institute), Goethe University, Frankfurt am Main, Germany (P.B., T.S., L.J., A.K.B., Mi.M.); Institute of Medical Virology, Goethe University, Frankfurt am Main, Germany (Ma.M., F.R., H.F.R., A.B., R.A., J.C.); German Cancer Consortium, Heidelberg, Germany (J.P.S., Mi.M.); German Cancer Research Center, Heidelberg, Germany (J.P.S., Mi.M.); Department of Neurosurgery, Goethe University, Frankfurt am Main, Germany (K.F., V.S.); Senckenberg Institute of Neurooncology, University of Frankfurt am Main, Germany (K.F., J.P.S.).
authors.forename: Jindrich
authors.initials: J
authors.lastname: Cinatl
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000401:mortality / Q000821:virology; D016022:Case-Control Studies; D003587:Cytomegalovirus / Q000235:genetics / Q000302:isolation & purification*; D003586:Cytomegalovirus Infections / Q000175:diagnosis* / Q000453:epidemiology / Q000401:mortality / Q000821:virology; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D005500:Follow-Up Studies; D005909:Glioblastoma / Q000175:diagnosis* / Q000453:epidemiology / Q000401:mortality / Q000821:virology; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000175:diagnosis* / Q000453:epidemiology / Q000401:mortality / Q000821:virology; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D016036:Seroepidemiologic Studies; D015996:Survival Rate
chemical_list: D004279:DNA, Viral
keywords: cytomegalovirus; glioma; oncomodulation