title: Expression of Epstein-Barr virus-encoded proteins in extranodal NK/T-cell Lymphoma, nasal type (ENKL): differences in biologic and clinical behaviors of LMP1-positive and -negative ENKL.
abstract: OBJECTIVE
  Extranodal NK/T-cell lymphoma, nasal type (ENKL) is closely associated with Epstein-Barr virus (EBV). To elucidate its pathogenetic role, we examined the expression profiles of EBV-encoded proteins, especially focusing on latent membrane protein 1 (LMP1).
  
  
  METHODS
  Immunohistochemistry was carried out using clinical samples from ENKL cases, which were diagnosed between 1996 and 2010 at our institution. We statistically assessed the correlation between LMP1 positivity and the clinicopathologic data and further examined phosphorylation status of NF-κB RelA and Akt in ENKL cell lines.
  
  
  RESULTS
  Most of the 30 examined cases showed pleomorphic morphology, natural killer cell immunophenotype, and a localized disease. Immunohistochemistry detected EBERs, but not EBNA2, in all cases. LMP1 and LMP2A were positive in 22 (73.3%) and 12 cases (40.0%), respectively. LMP1-positive cases tended to show a localized disease (P = 0.060, the Fisher exact test). Nuclear localization of phosphorylated RelA and detection of phosphorylated Akt were predominantly observed in LMP1-positive cases (P = 0.002 and P < 0.001, respectively, the Fisher exact test). RNA silencing experiments of LMP1 in Hank1 cells suggested a positive correlation between LMP1 expression and phosphorylation of RelA and Akt. With a median follow-up period of 26.7 months (range, 0.2-142.3 months), the 2.5-year overall survival rates for LMP1-positive and -negative cases were estimated at 78.3% and 12.5%, respectively (P = 0.001, log-rank test).
  
  
  CONCLUSIONS
  LMP1 expression shows correlations with phosphorylation of RelA and Akt and possibly has a favorable impact on clinical outcome in ENKL.
authors.affiliation: Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Kanemitsu
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Isobe
authors.forename: Azuchi
authors.initials: A
authors.lastname: Masuda
authors.forename: Shuji
authors.initials: S
authors.lastname: Momose
authors.forename: Morihiro
authors.initials: M
authors.lastname: Higashi
authors.forename: Jun-ichi
authors.initials: J
authors.lastname: Tamaru
authors.forename: Koichi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Norio
authors.initials: N
authors.lastname: Komatsu
mesh_terms: D000328:Adult; D000368:Aged; D045744:Cell Line, Tumor; D020031:Epstein-Barr Virus Infections / Q000235:genetics / Q000821:virology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000096:biosynthesis; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D006801:Humans; D007150:Immunohistochemistry; D054391:Lymphoma, Extranodal NK-T-Cell / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins / Q000096:biosynthesis; D012269:Ribosomal Proteins / Q000096:biosynthesis; D051996:Transcription Factor RelA / Q000378:metabolism; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014764:Viral Proteins / Q000096:biosynthesis
chemical_list: C402641:EBNA-2 protein, Human herpesvirus 4; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; C498143:RELA protein, human; D034741:RNA, Small Interfering; D016601:RNA-Binding Proteins; D012269:Ribosomal Proteins; D051996:Transcription Factor RelA; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C067169:RPL22 protein, human; D051057:Proto-Oncogene Proteins c-akt