* Context.-Epstein-Barr virus (EBV) has been classically associated with 3 malignancies, Burkitt lymphoma, B-cell lymphoproliferative syndromes, and nasopharyngeal carcinoma, and more recently with Hodgkin disease, T-cell lymphomas, and gastric and breast carcinomas, as well as with leiomyosarcoma and leiomyoma associated with immunosuppression.
Objective.-To compare EBV expression in Argentine tumor samples with those reported elsewhere, we analyzed EBV expression in an Argentine pediatric population with non-Hodgkin lymphoma and correlated these results with clinical course and outcome.
Methods.-We studied EBV presence by latent membrane protein-1 protein labeling by immunohistochemistry, by in situ hybridization, and by polymerase chain reaction for Epstein-Barr-encoded RNAs (EBERs) in formalin-fixed and paraffin-embedded non-Hodgkin lymphoma tissue samples (collected retrospectively) from 32 pediatric patients at Ricardo Gutierrez Children's Hospital from 1993 to 2000.
Results.-Eight out of the 32 (25%) non-Hodgkin lymphoma cases showed latent membrane protein-I and EBERs by in situ hybridization positive staining in tumor cells. Among EBERs and latent membrane protein-l-positive cases, there were 5 immunocompromised patients, with either human immunodeficiency virus infection or primary immunodeficiency. The EBERs in situ hybridization results were confirmed by EBERs polymerase chain reaction in good-quality DNA from 11 samples, with 3 proving positive and 8 negative.
Conclusions.-The association of EBV with non-Hodgkin lymphoma in the Argentine pediatric population was low (25%), and this figure rose to 100% when only the immunocompromised patients subgroup was considered, confirming that the virus is probably a cofactor in the lymphomagenesis of some but not all pediatric non-Hodgkin lymphoma. So far, no differences in clinical outcome are discernible between EBV-positive and EBV-negative nonHodgkin lymphoma patients.
(Arch Pathol Lab Med. 2002;126:331-335)
Epstein-Barr virus (EBV) is one of 8 known human herpesviruses. It infects the vast majority of mankind, with a prevalence in the total population ranging from 80% to 90%,1 and although it is etiologically associated with several diseases, by and large it establishes a lifelong silent infection.2
Latent membrane protein-1 (LMP-1) and Epstein-Barr nuclear antigen-2 (EBNA-2) are the 2 EBV latency proteins associated with cellular growth regulation. It is well known that LMP-1 exerts transforming effects on continuous rodent fibroblast cell lines' and that it also protects against apoptosis by enhancing expression of the bcl-2 proto-oncogene.3
Two EBV types circulate in most human populations, types 1 and 2, which differ only in a few latency genes, particularly nuclear antigens EBNA-2, EBNA-3a, EBNA-3b, and EBNA-3c. Epstein-Barr virus type 1 is more common in developed countries, whereas EBV type 2 is more prevalent in Africa. In addition, type 1 has proven in vitro to be a more potent transformer of B cells than type 2.1
In recent years, serologic and molecular assays have provided evidence that EBV is associated with several malignancies. Besides Burkitt lymphoma, EBV is now suspected as a pathogenic agent in other non-Hodgkin lymphomas (eg, acquired immune deficiency syndrome [AIDS]-associated, posttransplant, and nasal T/natural killer cell), Hodgkin lymphoma, nasopharyngeal carcinoma, lymphoepithelioma-like carcinoma, and gastric adenocarcinoma, as well as leiomyosarcoma and leiomyoma associated with immunosuppression. Because EBV-related malignancies may occur throughout life, the epidemiology of primary EBV infection, particularly its age at onset, has a potential relevance to understanding the etiology of these cancers.4
Lymphomas constitute approximately 10% of all childhood cancers in developed countries; the incidence of non-- Hodgkin lymphomas (NHL) increases steadily throughout life, and children younger than 16 years of age account for only 3% of all patients with NHL. Pediatric NHL may be divided into 3 major histologic categories, as follows: lymphoblastic lymphoma, Burkitt lymphoma, and large cell lymphoma.5
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Paola A. Chabay; Elena N. De Matteo, MD; Luis Aversa, MD; Silvana Maglio, MD; Saul Grinstein, Md; Maria Victoria Preciado, PhD
Accepted for publication September 26, 2001.
From the Virology Laboratory (Ms Chabay and Drs Grinstein and Preciado), the Pathology Department (Drs De Matteo and Maglio), and the Hematology Department (Dr Aversa), Ricardo Gutierrez Children's Hospital, Buenos Aires, Argentina.
Reprints: Maria Victoria Preciado, PhD, Laboratorio de Virologia, Hospital de Ninos Ricardo Gutierrez, Gallo 1330, C1425EFD Ciudad de Buenos Aires, Argentina (e-mail: preciado@conicet.gov.ar).
Copyright College of American Pathologists Mar 2002
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