ABSTRACT
BACKGROUND: Pediatric nasopharyngeal carcinoma (NPC) is relatively rare. The Epstein Barr virus (EBV) association with the oncogenesis of NPC is well established. Apoptosis-related proteins, p53 and bcl-2, have also been described in adult NPC pathogenesis. PROCEDURE: From 1988 to 1998, 16 patients with NPC were treated at R. Gutierrez Children's Hospital and the National J.P. Garrahan Pediatric Hospital. Their median age was 12 years (range 8-20), 2 females and 14 males. The presence of p53, bcl-2 and latent membrane protein-1 (LMP-1) of EBV expression was studied by immunohistochemistry and Epstein Barr encoded RNAs (EBERs) by in situ hybridization in tissue sections from formalin-fixed, paraffin-embedded NPC biopsies RESULTS: EBV presence and LMP-1 expression in epithelial tumor cells were detected in all the biopsies studied. p53 was expressed in 13/16 NPCs, but the frequency of positive malignant cells differed from case to case, ranging from less than 25 to 100% with heterogeneous staining intensity. Bcl-2 positive staining in tumor epithelial cells was detected in 2/16; whereas 10/16 cases showed bcl-2 positivity in infiltrating lymphocytes. CONCLUSIONS: Although our series is small, we conclude that the pathogenesis of pediatric NPC as a multistep process may well involve EBV infection. This leads to LMP-1 expression and p53 overexpression in epithelial tumor cells, whereas bc-2 seems unrelated to the development of this disorder.
Subject(s)
Carcinoma/genetics , Carcinoma/virology , DNA, Neoplasm/genetics , Epstein-Barr Virus Infections/complications , Gene Expression Regulation, Neoplastic , Nasopharyngeal Neoplasms/genetics , Nasopharyngeal Neoplasms/virology , Proto-Oncogene Proteins c-bcl-2/biosynthesis , Tumor Suppressor Protein p53/biosynthesis , Viral Matrix Proteins/biosynthesis , Adolescent , Adult , Child , Female , Humans , Immunohistochemistry , In Situ Hybridization , Male , RNAABSTRACT
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 Gutiérrez Children's Hospital from 1993 to 2000. RESULTS: Eight out of the 32 (25%) non-Hodgkin lymphoma cases showed latent membrane protein-1 and EBERs by in situ hybridization positive staining in tumor cells. Among EBERs and latent membrane protein-1-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 non-Hodgkin lymphoma patients.
