Prognostic Significance of the Epstein-Barr Virus, p53, Bcl-2, and Survivin in Nasopharyngeal Cancer
| Autor: | Fei-Fei Liu, Wei Shi, Derek Wong, Melania Pintilie, Joseph D. Mocanu, Christine MacMillan, Patrick J. Gullane, Brian O'Sullivan, Carlo Bastianutto, Joseph D. Martin, Kenneth W. Yip |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Epstein-Barr Virus Infections Herpesvirus 4 Human Cancer Research Survivin Biology medicine.disease_cause Herpesviridae Inhibitor of Apoptosis Proteins Immunoenzyme Techniques Biopsy Carcinoma medicine Humans Gammaherpesvirinae Survival rate medicine.diagnostic_test Nasopharyngeal Neoplasms DNA Neoplasm Middle Aged Prognosis medicine.disease biology.organism_classification Epstein–Barr virus Neoplasm Proteins Gene Expression Regulation Neoplastic Survival Rate Proto-Oncogene Proteins c-bcl-2 Oncology Carcinoma Squamous Cell Cancer research Immunohistochemistry Female Tumor Suppressor Protein p53 Microtubule-Associated Proteins |
| Zdroj: | Clinical Cancer Research. 12:5726-5732 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-06-0571 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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