Expression of Epstein-Barr virus-encoded latent membrane protein (LMP-1), p16 and p53 proteins in nonendemic nasopharyngeal carcinoma (NPC): a clinicopathological study

Arch Med Res. 2014 Apr;45(3):229-36. doi: 10.1016/j.arcmed.2014.02.002. Epub 2014 Mar 4.

Abstract

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 χ(2) 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.

Keywords: EBV-LMP1; Immunohistochemistry; Nasopharyngeal carcinoma; p16; p53.

MeSH terms

  • Adult
  • Aged
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Epstein-Barr Virus Infections / metabolism*
  • Epstein-Barr Virus Infections / pathology
  • Female
  • Herpesvirus 4, Human / genetics*
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Nasopharyngeal Carcinoma
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / pathology
  • Neoplasm Recurrence, Local
  • Retrospective Studies
  • Sex Factors
  • Tumor Suppressor Protein p53 / metabolism*
  • Viral Matrix Proteins / genetics
  • Viral Matrix Proteins / metabolism*
  • Young Adult

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Tumor Suppressor Protein p53
  • Viral Matrix Proteins