title: Detection of Epstein-Barr virus nucleic acid sequences and protein in nodal T-cell lymphomas: relation between latent membrane protein-1 positivity and clinical course.
abstract: Forty-six nodal T-cell lymphomas, classified according to the updated Kiel classification, were investigated for the presence of Epstein-Barr virus (EBV) DNA by polymerase chain reaction (PCR), EBER 1 and 2 (EBER 1/2) and latent membrane protein-1 (LMP-1) expression. A combination of RNA in situ hybridization and immunohistochemistry was used to establish the phenotype of the Epstein-Barr virus harbouring cells. In 21 of 45 cases Epstein-Barr virus DNA sequences could be detected with the polymerase chain reaction. In 15 cases (14 of 21 EBV PCR positive cases), EBER 1/2 positive cells could be demonstrated. As judged by morphology, EBER 1/2 expression was found in nonneoplastic and neoplastic lymphoid cells. Double staining revealed that more than 80% of the EBER 1/2 harbouring cells, lacked B-, T- or histiocytic markers, suggesting down regulation of T- and B-cell markers by Epstein-Barr virus. In eight of 15 cases some EBER 1/2 positive T-cells (CD3, CD45RO, CD43) morphologically resembling tumour cells were found. In nine of 14 cases tested EBER 1/2 positive non-neoplastic B-cells (CD20) were seen. Based on in situ hybridization results, four patterns of EBER 1/2 positive cells were found, i.e. single cells (< 1 per medium power field (mpf), n = 3), scattered (1-25/mpf, n = 4), clustered (26-100/mpf, n = 5) and diffuse (> 100/mpf, n = 3). In eight of 15 cases a clustered or diffuse pattern of EBER 1/2 positive cells was found and these lymphomas were therefore considered to be strongly associated with Epstein-Barr virus. In these lymphomas LMP-1 expression was found to be associated with an aggressive clinical course and hepatosplenomegaly.
authors.affiliation: Department of Pathology, Free University Hospital, Amsterdam, The Netherlands.
authors.forename: P C
authors.initials: PC
authors.lastname: De Bruin
authors.forename: N M
authors.initials: NM
authors.lastname: Jiwa
authors.forename: P
authors.initials: P
authors.lastname: Van der Valk
authors.forename: P
authors.initials: P
authors.lastname: Van Heerde
authors.forename: R
authors.initials: R
authors.lastname: Gordijn
authors.forename: G J
authors.initials: GJ
authors.lastname: Ossenkoppele
authors.forename: J M
authors.initials: JM
authors.lastname: Walboomers
authors.forename: C J
authors.initials: CJ
authors.lastname: Meijer
mesh_terms: D004854:Herpesvirus 4, Human / Q000737:chemistry* / Q000302:isolation & purification; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017403:In Situ Hybridization; D008198:Lymph Nodes / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000382:microbiology*; D009856:Oncogene Proteins, Viral / Q000032:analysis* / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis*; D012367:RNA, Viral / Q000032:analysis*; D014763:Viral Matrix Proteins / Q000032:analysis* / Q000096:biosynthesis
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D009856:Oncogene Proteins, Viral; D012333:RNA, Messenger; D012367:RNA, Viral; D014763:Viral Matrix Proteins