Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma.
BACKGROUND
The Epstein-Barr virus (EBV) is consistently detected in patients with nasopharyngeal carcinoma. To determine whether EBV infection is an early, initiating event in the development of this malignant tumor, we screened nasopharyngeal-biopsy samples, most of which were archival, for preinvasive lesions, including dysplasia and carcinoma in situ. Preinvasive lesions were found in 11 samples, which were tested for the presence of EBV.


METHODS
EBV infection was detected with in situ hybridization for EBV-encoded RNAs (EBERs) and by immunohistochemical staining for latent membrane protein 1 (LMP-1). The larger samples were also tested for the EBV genome with the use of Southern blotting. The expression of specific EBV RNAs was determined by the amplification of complementary DNA with the polymerase chain reaction.


RESULTS
Evidence of EBV infection was detected in all 11 tissue samples with dysplasia or carcinoma in situ. EBERs were identified in all eight samples tested, and LMP-1 was detected in all six of the tested samples. Six of the seven samples tested for the EBV termini contained clonal EBV DNA: Transcription of the latent EBV gene products, EBV nuclear antigen 1, LMP-1, LMP-2A, and the BamHI-A fragment, was detected in most of the samples. Viral proteins characteristic of lytic lesions were not detected.


CONCLUSIONS
Preinvasive lesions of the nasopharynx are infected with EBV. The EBV DNA is clonal, indicating that the lesions represent a focal cellular growth that arose from a single EBV-infected cell and that EBV infection is an early, possibly initiating event in the development of nasopharyngeal carcinoma. Preinvasive lesions contain EBV RNAs that are characteristic of latent infection but not the viral proteins that are characteristic of lytic infection. The detection of the EBV-transforming gene, LMP-1, in all the neoplastic cells suggests that its expression is essential for preinvasive epithelial proliferations associated with nasopharyngeal carcinoma.
Pathmanathan
R
R
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599-7295, USA.
Prasad
U
U
Sadler
R
R
Flynn
K
K
Raab-Traub
N
N
D000956:Antigens, Viral / Q000032:analysis; D015139:Blotting, Southern; D002278:Carcinoma in Situ / Q000737:chemistry / Q000821:virology; D002999:Clone Cells; D006566:Herpesviridae Infections / Q000150:complications / Q000175:diagnosis*; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D006965:Hyperplasia / Q000473:pathology / Q000821:virology; D017403:In Situ Hybridization; D009303:Nasopharyngeal Neoplasms / Q000737:chemistry / Q000473:pathology / Q000821:virology*; D009305:Nasopharynx / Q000473:pathology* / Q000821:virology; D011230:Precancerous Conditions / Q000737:chemistry / Q000821:virology*; D012367:RNA, Viral / Q000302:isolation & purification*; D014158:Transcription, Genetic; D014412:Tumor Virus Infections / Q000150:complications / Q000175:diagnosis*; D014763:Viral Matrix Proteins / Q000032:analysis
D000956:Antigens, Viral; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D012367:RNA, Viral; D014763:Viral Matrix Proteins