title: Prognostic significance of the Epstein-Barr virus, p53, Bcl-2, and survivin in nasopharyngeal cancer.
abstract: OBJECTIVE
  Nasopharyngeal cancer (NPC) is a malignant epithelial carcinoma which is intimately associated with EBV. The latent presence of EBV affects the function of p53, Bcl-2, and survivin. We thus investigated the relationship between EBV status, p53, Bcl-2, and survivin in biopsy specimens from patients with primary NPC.
  
  
  METHODS
  Archival formalin-fixed, paraffin-embedded NPC biopsies were evaluated in 80 patients treated with curative radiation from a single institution. The presence of EBV was determined using EBER in situ hybridization, whereas p53, Bcl-2, and survivin were assessed using immunohistochemistry.
  
  
  RESULTS
  The majority of NPC specimens in this patient cohort were EBER-positive (64 of 78, or 82%), which in turn, was significantly associated with ethnicity (P = 0.0007), and WHO subtype 2A/2B (P = 0.04). EBER-positive tumors were also associated with p53 (P = 0.002), Bcl-2 (P = 0.04), and nuclear survivin (P = 0.03) expression. Patients with EBER-positive NPC fared better, with a 10-year overall survival of 68% versus 48% for EBER-negative patients (P = 0.03). For nuclear survivin, patients with either low or high nuclear survivin fared worse than patients with intermediate survivin expression (P = 0.05), suggesting that there is an optimal proportion of survivin-expressing cells for best function and clinical outcome.
  
  
  CONCLUSIONS
  With an extended median follow-up time of 11.4 years, EBV status remains a strong predictor for overall survival in NPC. EBV-positive NPC has strong molecular associations with p53, Bcl-2, and survivin expression. Furthermore, we provide clinical data revealing the potentially dual nature of survivin in predicting clinical outcome.
authors.affiliation: Department of Medical Biophysics, University of Toronto, and Division of Applied Molecular Oncology, Ontario Cancer Institute, 610 University Avenue, Toronto, Ontario, Canada.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Yip
authors.forename: Wei
authors.initials: W
authors.lastname: Shi
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Martin
authors.forename: Joseph D
authors.initials: JD
authors.lastname: Mocanu
authors.forename: Derek
authors.initials: D
authors.lastname: Wong
authors.forename: Christine
authors.initials: C
authors.lastname: MacMillan
authors.forename: Pat
authors.initials: P
authors.lastname: Gullane
authors.forename: Brian
authors.initials: B
authors.lastname: O'Sullivan
authors.forename: Carlo
authors.initials: C
authors.lastname: Bastianutto
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Liu
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000821:virology; D004273:DNA, Neoplasm / Q000235:genetics; D020031:Epstein-Barr Virus Infections / Q000378:metabolism* / Q000821:virology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D007124:Immunoenzyme Techniques; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000821:virology; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015996:Survival Rate; D000077022:Survivin; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: C107489:BIRC5 protein, human; D004273:DNA, Neoplasm; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D016159:Tumor Suppressor Protein p53