title: Prognostic role of Ebstein-Barr virus latent membrane protein-1 and interleukin-10 expression in patients with nasopharyngeal carcinoma.
abstract: OBJECTIVE
  We aimed to investigate Ebstein-Barr virus (EBV) latent membrane protein-1 (LMP-1) and Interleukine-10 (IL-10) expression in nasopharyngeal carcinoma (NPC) patients and to evaluate their prognostic significance.
  
  
  METHODS
  Between 1993 and 1999, 166 patients were treated with the diagnosis of nonmetastatic NPC at our department. The expression of LMP-1 and IL-10 was investigated by using an immunohistochemical approach in 74 (53 male, 21 female) patients whose paraffin embedded tissue samples were available. A detailed histopathological analysis including degree of apoptosis and lymphocyte infiltration was made and all patients were reclassified according to the World Health Organization (WHO) classification. Univariate, multivariate, and logistic regression analyses were performed using all clinical and pathological prognostic factors. All patients were treated with radiotherapy +/- chemotherapy. Follow-up ranged between 12 and 80 months (median: 32).
  
  
  RESULTS
  The histopathological diagnosis was WHO-I in 1 (1.3%), WHO-II in 15 (20.2%), and WHO-III in 58 (79.5%) patients. There were 38 (51%) patients with IL-10 expression and 44 (61%) patients with LMP-1 expression. Twenty-seven (36.4%) patients were found to be both IL-10 and LMP-1 positive. There were significantly more N0 disease in patients without LMP-1 expression compared to LMP-1 positive patients (65% vs. 35%, p = 0.01). The logistic regression analysis showed advanced nodal involvement to be the major parameter affecting the expression of IL-10 (p = 0.03). Three-year overall survival (OS), locoregional relapse free survival (LRRFS), and distant metastasis free survival (DMFS) rates were 67.8%, 84.4%, and 74.3%, respectively, for the whole group. On univariate analysis, LRRFS was significantly lower in WHO-III patients, DMFS was significantly lower in advanced nodal disease and IL-10 negative patients, and OS was significantly lower in WHO-III patients. Multivariate analysis showed that WHO-III and T2 patients were significantly associated with lower OS and N3 patients were significantly associated with lower DMFS.
  
  
  CONCLUSIONS
  We observed a high rate (61%) of EBV (LMP-1 positive) and NPC association in our patients. LMP-1 positive tumors were found to be more prone to invade lymph nodes. Patients with negative IL-10 expression had more advanced N disease. We did not find a prognostic significant role of IL-10 and EBV LMP-1 on survival in multivariate analysis.
authors.affiliation: Department of Radiation Oncology, Hacettepe University, Faculty of Medicine, Ankara, Turkey. eozyar@hacettepe.edu.tr
authors.forename: Enis
authors.initials: E
authors.lastname: Ozyar
authors.forename: Ayşe
authors.initials: A
authors.lastname: Ayhan
authors.forename: Aylin F
authors.initials: AF
authors.lastname: Korcum
authors.forename: I Lale
authors.initials: IL
authors.lastname: Atahan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D002277:Carcinoma / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D002648:Child; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D009362:Neoplasm Metastasis; D011379:Prognosis; D016019:Survival Analysis; D014763:Viral Matrix Proteins / Q000032:analysis*
chemical_list: C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins; D016753:Interleukin-10