Molecular characterization of Epstein-Barr virus and oncoprotein expression in nasopharyngeal carcinoma in Korea

Head Neck. 2004 Jul;26(7):573-83. doi: 10.1002/hed.10370.

Abstract

Background: We evaluated the characteristics of nasopharyngeal carcinoma in Korea, including its clinical, pathologic, and molecular features, especially emphasizing on the EBV strains involved, latent membrane protein 1 (LMP1) expression, and the alterations of matrix metalloproteinase 9 (MMP9) and E-cadherin expression. METHODS.: The presence of EBV was evaluated by EBER in situ hybridization, and the expression of LMP1, MMP9, and E-cadherin by immunohistochemistry. The characterization of EBV type and LMP1 variant was performed by PCR.

Results: EBER was detected in 55 of 57 cases (96%) of nonkeratinizing carcinoma (NKC) and undifferentiated carcinoma, but in only four of nine cases (44%) of squamous cell carcinoma (SCC). EBER positivity was much higher in the group with nodal metastases (p =.003). The predominant strain of EBV infection was type A (81%) and a 30-bp deletion LMP1 variant (77%). All EBER-positive SCCs were infected with EBV type A. LMP1 expression was detected in 36 of 59 (61%) patients with latent EBV infection and MMP9 in 41 of these 59 (69%). LMP1 positivity was much higher among the patients aged 50 years and younger. MMP9 expression was associated with LMP1 expression (p =.008), and nodal and distant metastasis (p =.019, p =.045). Loss of E-cadherin expression was correlated with MMP9 and nodal metastasis. The survival rate was much lower in patients with a higher TNM classification, stage, and a histology of SCC. EBER positivity was associated with a better prognosis in the Kaplan-Meier test, but had no prognostic value by Cox regression analysis. Loss of E-cadherin expression and nodal metastasis were also correlated with local recurrence and distant metastasis.

Conclusion: EBV type and LMP1 variant had no significant influence on the clinicopathologic properties of tumor. However, there was a tendency toward a better survival in the EBV type B group. Histology and clinical staging were the two most important prognostic factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Asian Continental Ancestry Group / genetics
  • Cadherins / metabolism*
  • Cytoplasm / metabolism
  • Epstein-Barr Virus Infections / epidemiology
  • Epstein-Barr Virus Infections / metabolism*
  • Female
  • Herpesvirus 4, Human / genetics*
  • Herpesvirus 4, Human / physiology
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Korea / epidemiology
  • Male
  • Matrix Metalloproteinase 9 / metabolism*
  • Middle Aged
  • Nasopharyngeal Neoplasms / epidemiology
  • Nasopharyngeal Neoplasms / metabolism*
  • Nasopharyngeal Neoplasms / mortality
  • Nasopharyngeal Neoplasms / virology*
  • Neoplasm Staging
  • Oncogene Proteins, Viral / metabolism*
  • Polymerase Chain Reaction
  • Seroepidemiologic Studies
  • Survival Analysis
  • Viral Matrix Proteins / metabolism*
  • Virus Latency

Substances

  • Cadherins
  • EBV-associated membrane antigen, Epstein-Barr virus
  • Oncogene Proteins, Viral
  • Viral Matrix Proteins
  • Matrix Metalloproteinase 9