Expression of Epstein-Barr Virus-encoded Latent Membrane Protein (LMP-1), p16 and p53 Proteins in Nonendemic Nasopharyngeal Carcinoma (NPC): A Clinicopathological Study

Abstract

Although the latent membrane protein type 1 (LMP1) is frequently expressed in Epstein-Barr virus (EBV) malignancies, its contribution to the pathogenesis of nasopharyngeal carcinoma (NPC) is not fully defined. LMP1 functions as a viral mimic of the TNFR family member engaging a number of signaling pathways that induce morphological and phenotypic alterations. This study aimed to investigate the LMP1 expression and EBV infection in relation to clinical outcome and survival in a series of Mexican NPC patients. We also studied expression of p16 and p53 proteins. We analyzed in 25 tumor specimens the expression of LMP1, p16 and p53 by immunohistochemistry (IHC) and EBV presence by IHC/in situ hybridization. Differences in clinical outcome and survival in relation to protein expression were correlated through χ(2) statistics and Kaplan-Meier survival curves. Our results showed a rate of 92% (23/25) of EBV infection. The expressions of LMP-1, p16 and p53 proteins were 40.0, 44.0 and 40.0%, respectively. LMP-1 immunoexpression was more common in older patients (>50 vs. <50 years old, p = 0.02) and with parapharyngeal space invasion (p = 0.02). The presence of metastatic disease at diagnosis (p = 0.03), distant recurrence disease (p = 0.006) and shorter distance recurrence-free survival (p = 0.05) was associated with lack of p16. In our series, EBV infection rates are particularly high for nonendemic NPC, although without a statistically significant difference in overall survival, LMP1 and p16 expression was correlated with poorer clinical prognosis. Probably, LMP1 and p16 detection identify a worse clinical prognosis in NPC patient subgroup.