PLOS ONE_8_2_e56741.pdf 287 KB
Ando, Midori Okayama Univ, Dept Pathol, Grad Sch Med Dent & Pharmaceut Sci
Sato, Yasuharu Okayama Univ, Dept Pathol, Grad Sch Med Dent & Pharmaceut Sci ORCID Kaken ID researchmap
Takata, Katsuyoshi Okayama Univ, Dept Pathol, Grad Sch Med Dent & Pharmaceut Sci Kaken ID
Nomoto, Junko Natl Canc Ctr, Div Hematol
Nakamura, Shigeo Nagoya Univ Hosp, Dept Pathol & Clin Lab
Ohshima, Koichi Kurume Univ, Sch Med, Dept Pathol
Takeuchi, Tamotsu Gifu Univ, Grad Sch Med, Dept Immunopathol
Orita, Yorihisa Okayama Univ, Dept Otolaryngol Head & Neck Surg, Grad Sch Med Dent & Pharmaceut Sci
Kobayashi, Yukio Natl Canc Ctr, Div Hematol
A negative regulator of the nuclear factor (NF)-kappa B pathway, A20 (TNFAIP3), is inactivated in several types of lymphomas; particularly in diffuse large B-cell lymphoma (DLBCL), classical Hodgkin's lymphoma, and extranodal marginal zone lymphoma of the mucosa-associated lymphoid tissue. These findings suggest that the NF-kappa B activation is related to A20 inactivation. Recently, A20 inactivation has also been observed in Epstein-Barr virus (EBV)-related lymphomas; however, this occurrence has not been well investigated. Moreover, NF-kappa B is a key molecule in activated B-cell-like (ABC)-type DLBCL; EBV-associated DLBCL is of the ABC type. Therefore, we focused on A20 deletions in EBV-associated lymphoproliferative disorders/lymphomas. Using fluorescent in situ hybridization analysis, A20 deletions were identified in 4 of 13 samples from patients with pyothorax-associated lymphoma (PAL) (31%), 3 of 20 samples from nasal-type NK/T cell lymphomas (NKTLs) (15%), 1 of 8 samples of EBV-positive DLBCL of the elderly (DLBCL-e) (13%), but not in any of the 11 samples from individuals with methotrexate-related lymphoproliferative disorder (MTX-LPD) (0%). Among the samples with A20 deletions, EBV latent membrane protein 1 (LMP-1) expression was detected in all 4 of the PAL samples with A20 deletions and in the DLBCL-e sample with an A20 deletion, but not in any of the 3 NKTL samples. This finding indicated that A20 deletions were not directly related to the EBV latency pattern of lymphomas, although such deletions might be related to the diagnostic category. Immunohistologically, the A20 protein was absent in 2 (15%) of the13 PAL samples, 1 (9%) of 11 MTX-LPD samples, and in none of the 20 NKTL (0%) or 8 DLBCL-e samples. In conclusion, A20 deletion and/or dysfunctional expression are frequently associated with PALs, and A20 abnormalities may be related to the pathogenesis of PAL.
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© 2013 Ando et al.
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