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


CONCLUSIONS
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.
Jeon
Yoon Kyung
YK
Department of Pathology and Cancer Research Center, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul 110-799, Korea.
Lee
Bo Young
BY
Kim
Ji Eun
JE
Lee
Seung Sook
SS
Kim
Chul Woo
CW
D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics; D015820:Cadherins / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D020031:Epstein-Barr Virus Infections / Q000453:epidemiology / Q000378:metabolism*; D005260:Female; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007723:Korea / Q000453:epidemiology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009303:Nasopharyngeal Neoplasms / Q000453:epidemiology / Q000378:metabolism* / Q000401:mortality / Q000821:virology*; D009367:Neoplasm Staging; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D016036:Seroepidemiologic Studies; D016019:Survival Analysis; D014763:Viral Matrix Proteins / Q000378:metabolism*; D017735:Virus Latency
D015820:Cadherins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D009856:Oncogene Proteins, Viral; D014763:Viral Matrix Proteins; D020780:Matrix Metalloproteinase 9