title: Human cytomegalovirus tegument protein pp65 is detected in all intra- and extra-axial brain tumours independent of the tumour type or grade.
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.
authors.affiliation: Department of Pathology, Uppsala University Hospital, Uppsala, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Sylwia
authors.initials: S
authors.lastname: Libard
authors.affiliation: Department of Pathology, Uppsala University Hospital, Uppsala, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Svetlana N
authors.initials: SN
authors.lastname: Popova
authors.affiliation: Department of Pathology, Uppsala University Hospital, Uppsala, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Rose-Marie
authors.initials: RM
authors.lastname: Amini
authors.affiliation: Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Vesa
authors.initials: V
authors.lastname: Kärjä
authors.affiliation: Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Timo
authors.initials: T
authors.lastname: Pietiläinen
authors.affiliation: Department of Clinical Pathology, Kuopio University Hospital, Kuopio, Finland.
authors.forename: Kirsi M
authors.initials: KM
authors.lastname: Hämäläinen
authors.affiliation: Department of Pathology, Uppsala University Hospital, Uppsala, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.affiliation: Department of Neurosurgery, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Göran
authors.initials: G
authors.lastname: Hesselager
authors.affiliation: Department of Oncology, Centre for Research & Development, County Council of Gävleborg, Gävle Hospital, Gävle, Sweden; Department of radiation sciences, Umeå University, Umeå, Sweden.
authors.forename: Michael
authors.initials: M
authors.lastname: Bergqvist
authors.affiliation: Department of Radiology, Oncology and Radiation Science, Section of Oncology, Uppsala University, Uppsala, Sweden.
authors.forename: Simon
authors.initials: S
authors.lastname: Ekman
authors.affiliation: Department of Neurosurgery, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Zetterling
authors.affiliation: Department of Neuroscience Neurology, Uppsala University, Uppsala, Sweden.
authors.forename: Anja
authors.initials: A
authors.lastname: Smits
authors.affiliation: Department of Neurosurgery, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Pelle
authors.initials: P
authors.lastname: Nilsson
authors.affiliation: Department of Women's and Children's Health, Uppsala University, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Susan
authors.initials: S
authors.lastname: Pfeifer
authors.affiliation: Department of Oncology-Pathology, Karolinska Institutet, Cancer Center Karolinska, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Teresita Diaz
authors.initials: TD
authors.lastname: de Ståhl
authors.affiliation: Department of Radiology, Oncology and Radiation Science, Section of Oncology, Uppsala University, Uppsala, Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Enblad
authors.affiliation: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ponten
authors.affiliation: Department of Pathology, Uppsala University Hospital, Uppsala, Sweden; Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
authors.forename: Irina
authors.initials: I
authors.lastname: Alafuzoff
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000473:pathology / Q000821:virology*; D015331:Cohort Studies; D003587:Cytomegalovirus / Q000302:isolation & purification / Q000378:metabolism*; D005260:Female; D005909:Glioblastoma / Q000473:pathology / Q000821:virology; D006801:Humans; D007150:Immunohistochemistry; D008223:Lymphoma / Q000473:pathology / Q000821:virology; D008297:Male; D008527:Medulloblastoma / Q000473:pathology / Q000821:virology; D008579:Meningioma / Q000473:pathology / Q000821:virology; D008875:Middle Aged; D060787:Neoplasm Grading; D010750:Phosphoproteins / Q000032:analysis*; D014763:Viral Matrix Proteins / Q000032:analysis*; D055815:Young Adult
chemical_list: D010750:Phosphoproteins; D014763:Viral Matrix Proteins; C065418:cytomegalovirus matrix protein 65kDa