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

摘要

Background and Aims: 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. Methods: 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 χ2 statistics and Kaplan-Meier survival curves. Results: 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. Conclusions: 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.