Cytotoxic granular protein expression, Epstein-Barr virus strain type, and latent membrane protein-1 oncogene deletions in nasal T-lymphocyte/natural killer cell lymphomas from Mexico.
Nasal T-lymphocyte/natural killer cell lymphomas (nT/NKLs) are a distinct group of neoplasms highly associated with Epstein-Barr virus (EBV), with a high prevalence in Asia but rare in Western countries. Recent studies indicate that these neoplasms are of cytotoxic T- or NK-cell derivation. Previous studies identifying a characteristic 30-base pair deletion within the 3' end of latent membrane protein-1 (del-LMP-1) in other EBV-associated lymphomas suggested a pathogenetic role for del-LMP-1 in those neoplasms. We examined 23 cases of nT/NKL from Mexico for expression of the cytolytic granular proteins TIA-1 and perforin (PRF), and for the presence of EBV by in situ hybridization (ISH). Polymerase chain reaction was performed to identify the EBV (EBNA-2) strain type and the status of the LMP-1 gene (del-LMP-1). Controls consisted of 11 sinonasal B-cell lymphomas (nBLs) and 30 reactive tonsils (RTs) from healthy Mexican individuals. The nT/NKLs expressed TIA-1 in 21 (91%) of 23 cases and PRF in 15 (65%) of 23 cases. In contrast, all of the nBLs were negative for TIA-1 and PRF. Twenty-two (96%) of 23 nT/NKLs were positive for EBV by ISH. In contrast, only 2 (18%) of 11 nBLs were positive for EBV by ISH. EBV strain Type A was identified in 21 (91%) of 23 cases, whereas strain Type B was present in 2 (9%) of the 23 nT/NKLs. A similar percentage (80%) of Type A was noted in 12 of the 15 RTs. del-LMP-1 was detected in 6 (26%) of 23 nT/NKLs, comprising 4 cases of Type A and 2 of Type B. del-LMP-1 was detected in 9 (45%) of 20 RTs. Our results indicated that TIA-1 and PRF were sensitive markers of nT/NKL. The presence of del-LMP-1 in comparable frequencies in the RTs and nT/NKLs suggested to us that this genotype was common in the Mexican population and argued against a definite pathogenetic role for del-LMP-1 in nT/NKL.
Elenitoba-Johnson
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KS
Section of Hematopathology, Laboratory of Pathology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA.
Zarate-Osorno
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Meneses
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Krenacs
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Kingma
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Raffeld
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Jaffe
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D000293:Adolescent; D000328:Adult; D000368:Aged; D005260:Female; D017353:Gene Deletion; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007694:Killer Cells, Natural / Q000473:pathology; D016399:Lymphoma, T-Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008800:Mexico; D008875:Middle Aged; D009669:Nose Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D054353:Perforin; D039102:Poly(A)-Binding Proteins; D016133:Polymerase Chain Reaction; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D016601:RNA-Binding Proteins / Q000378:metabolism*; D000074019:T-Cell Intracellular Antigen-1; D014763:Viral Matrix Proteins / Q000235:genetics*
C037662:EBV-associated membrane antigen, Epstein-Barr virus; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D039102:Poly(A)-Binding Proteins; D052899:Pore Forming Cytotoxic Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; D000074019:T-Cell Intracellular Antigen-1; C071558:TIA1 protein, human; D014763:Viral Matrix Proteins; D054353:Perforin