text: Epstein-Barr virus-associated nonsmall cell lung carcinoma: undifferentiated "lymphoepithelioma-like" carcinoma as a distinct entity with better prognosis.
  BACKGROUND:
  Epstein-Barr virus (EBV) infection in nonsmall cell lung carcinoma (NSCLC) has been demonstrated in some ethnic groups. The pathobiology and the role of EBV and oncoprotein expression in these tumors have not been studied extensively. In this study, the authors investigated EBV-encoded RNA-1 (EBER1) transcripts by in situ hybridization and the expression of latent membrane protein-1 (LMP-1) and bcl-2 protein by immunohistochemistry in NSCLC patients from Taiwan, where nasopharyngeal carcinoma is endemic.
  METHODS:
  A total of 127 cases of NSCLC (43 cases of squamous cell carcinoma [SCC], 67 cases of adenocarcinoma [AD], 12 cases of large cell carcinoma [LCC], and 5 cases of lymphoepithelioma-like carcinoma [LE]) were included. A sensitive polymerase chain reaction-derived, digoxigenin-labeled DNA probe for in situ detection of EBER1 transcripts was performed for the detection of EBV. Immunohistochemistry using the avidin-biotin-immunoperoxidase method was also performed to evaluate the expression of bcl-2 and LMP-1.
  RESULTS:
  EBER1 was detected in 11 of the 127 NSCLC cases (8.7%; 6 SCC cases and 5 LE cases). All 5 LE cases were EBV-positive, whereas only 6 of the 43 SCC cases (14%), 0 of 67 AD cases, and 12 LCC cases were EBV-positive (P < 0.05). All five LE cases showed diffuse, strong, positive staining of tumor cells; five of the six SCC cases showed diffuse but weak staining. Among the nontumor epithelial cells, there was no EBER1 staining of any of the 11 EBER1-positive cases. The mean age of the LE patients was 10 years younger than that of the patients with other histological types. All 5 LE patients were nonsmokers, whereas 3 of the 6 patients with EBER1-positive SCC (50%) were smokers. EBER1 expression did not correlate with the 2-year survival rate of overall cases, but all 5 LE patients were alive without clinical evidence of disease at last follow-up. Gender, lymph node or distant metastasis, and clinical stage were not found to have any correlation with EBER1 expression (P > 0.05). All LE cases had bcl-2 oncoprotein expression (100%). This frequency was significantly different from other histologic types (P < 0.05). The LMP-1 detection rate was low and demonstrated no correlation with bcl-2 expression.
  CONCLUSIONS:
  In this study, the authors found that the primary LE of the lung is associated with young age, a history of not smoking, high bcl-2 immunoreactivity, and better survival rate. These characteristics demonstrate that EBV-associated LE of the lung is a unique entity. The findings of the current study suggest that EBV infection may play a different role in the tumorigenesis of primary LE of the lung than it does in other EBER1-positive NSCLCs.
  
entities: ['nonsmall cell lung carcinoma']
entities: Pathological_formation
entities: PMID-9635525_T1
entities: ['"lymphoepithelioma-like" carcinoma']
entities: Pathological_formation
entities: PMID-9635525_T2
entities: ['nonsmall cell lung carcinoma']
entities: Pathological_formation
entities: PMID-9635525_T3
entities: ['NSCLC']
entities: Pathological_formation
entities: PMID-9635525_T4
entities: ['tumors']
entities: Pathological_formation
entities: PMID-9635525_T5
entities: ['NSCLC']
entities: Pathological_formation
entities: PMID-9635525_T6
entities: ['nasopharyngeal carcinoma']
entities: Pathological_formation
entities: PMID-9635525_T7
entities: ['NSCLC']
entities: Pathological_formation
entities: PMID-9635525_T8
entities: ['squamous cell carcinoma']
entities: Pathological_formation
entities: PMID-9635525_T9
entities: ['SCC']
entities: Pathological_formation
entities: PMID-9635525_T10
entities: ['adenocarcinoma']
entities: Pathological_formation
entities: PMID-9635525_T11
entities: ['AD']
entities: Pathological_formation
entities: PMID-9635525_T12
entities: ['large cell carcinoma']
entities: Pathological_formation
entities: PMID-9635525_T13
entities: ['LCC']
entities: Pathological_formation
entities: PMID-9635525_T14
entities: ['lymphoepithelioma-like carcinoma']
entities: Pathological_formation
entities: PMID-9635525_T15
entities: ['LE']
entities: Pathological_formation
entities: PMID-9635525_T16
entities: ['SCC']
entities: Pathological_formation
entities: PMID-9635525_T17
entities: ['AD']
entities: Pathological_formation
entities: PMID-9635525_T18
entities: ['LCC']
entities: Pathological_formation
entities: PMID-9635525_T19
entities: ['LE']
entities: Pathological_formation
entities: PMID-9635525_T20
entities: ['LE']
entities: Pathological_formation
entities: PMID-9635525_T21
entities: ['SCC']
entities: Pathological_formation
entities: PMID-9635525_T22
entities: ['nontumor epithelial cells']
entities: Cell
entities: PMID-9635525_T23
entities: ['LE']
entities: Pathological_formation
entities: PMID-9635525_T24
entities: ['LE']
entities: Pathological_formation
entities: PMID-9635525_T25
entities: ['SCC']
entities: Pathological_formation
entities: PMID-9635525_T26
entities: ['LE']
entities: Pathological_formation
entities: PMID-9635525_T27
entities: ['lymph node']
entities: Multi-tissue_structure
entities: PMID-9635525_T28
entities: ['LE']
entities: Pathological_formation
entities: PMID-9635525_T29
entities: ['LE']
entities: Pathological_formation
entities: PMID-9635525_T30
entities: ['lung']
entities: Organ
entities: PMID-9635525_T31
entities: ['LE']
entities: Pathological_formation
entities: PMID-9635525_T32
entities: ['NSCLC']
entities: Pathological_formation
entities: PMID-9635525_T33
entities: ['SCC']
entities: Pathological_formation
entities: PMID-9635525_T34
entities: ['LE']
entities: Pathological_formation
entities: PMID-9635525_T35
entities: ['lung']
entities: Organ
entities: PMID-9635525_T36
entities: ['LE']
entities: Pathological_formation
entities: PMID-9635525_T37
entities: ['lung']
entities: Organ
entities: PMID-9635525_T38
entities: ['EBER1-positive NSCLCs']
entities: Pathological_formation
entities: PMID-9635525_T39
entities: ['tumor cells']
entities: Cell
entities: PMID-9635525_T40