title: Role and prognostic significance of proapoptotic proteins in Epstein-Barr virus-infected gastric carcinomas.
abstract: BACKGROUND
  The purposes of the present study were to evaluate the role and the prognostic values of proapoptotic proteins involved in the death receptors (Fas and TRAIL receptors) and mitochondrial pathways (Bax) in Epstein-Barr virus (EBV)-infected gastric carcinomas.
  
  
  METHODS
  Fifty-five EBV-infected gastric carcinomas were identified by in situ hybridization for EBV-encoded small RNAs. Immunohistochemistry was performed for Fas, Fas-ligand, FADD, TRAIL, DR4, DR5 and Bax. Apoptotic indices (AIs) were determined using TUNEL assay and assessed.
  
  
  RESULTS
  No remarkable differences in protein expressions were observed between EBV-infected gastric carcinomas and conventional gastric carcinomas. Bax positivity tended to be associated with higher AI (p = 0.068), whereas Fas and FADD positivities were related to lower AI (p = 0.006 and 0.059, respectively). Proteins involved in TRAIL pathways showed no statistical significant relationship with AI. TNM stage and Fas and FADD expressions were related to overall survival (p < 0.05), but TNM stage was the only independent prognostic factor.
  
  
  CONCLUSIONS
  Apoptosis in EBV-infected gastric carcinomas probably occurs via the mitochondrial pathway through Bax, rather than via the death receptor pathways. Fas and FADD expressions, and pathological tumor stage (TNM stage) may be the prognostic factors.
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, 28 Yongon-dong, Seoul 110-799, South Korea.
authors.forename: Mee Soo
authors.initials: MS
authors.lastname: Chang
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Eun Ji
authors.initials: EJ
authors.lastname: Jung
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Kim
authors.forename: Byung Lan
authors.initials: BL
authors.lastname: Lee
authors.forename: Woo Ho
authors.initials: WH
authors.lastname: Kim
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D020031:Epstein-Barr Virus Infections / Q000150:complications* / Q000378:metabolism* / Q000473:pathology; D053222:Fas Ligand Protein / Q000378:metabolism; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D015996:Survival Rate; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C494826:BAX protein, human; D053222:Fas Ligand Protein; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D051028:bcl-2-Associated X Protein