Prognostic significance of the Epstein-Barr virus, p53, Bcl-2, and survivin in nasopharyngeal cancer

Clin Cancer Res. 2006 Oct 1;12(19):5726-32. doi: 10.1158/1078-0432.CCR-06-0571.


Purpose: 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.

Experimental design: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / virology
  • DNA, Neoplasm / genetics
  • Epstein-Barr Virus Infections / metabolism*
  • Epstein-Barr Virus Infections / virology
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / isolation & purification
  • Humans
  • Immunoenzyme Techniques
  • Inhibitor of Apoptosis Proteins
  • Male
  • Microtubule-Associated Proteins / metabolism*
  • Middle Aged
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / virology
  • Neoplasm Proteins / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Survival Rate
  • Survivin
  • Tumor Suppressor Protein p53 / metabolism*


  • BIRC5 protein, human
  • DNA, Neoplasm
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Survivin
  • Tumor Suppressor Protein p53