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Previous Volume 333:693-698 September 14, 1995 Number 11 Next

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ABSTRACT

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 Bam HI-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.

Source Information

From the Lineberger Comprehensive Cancer Center (R.P., R.S., N.R.-T.) and the Department of Microbiology (R.S., N.R.-T.), University of North Carolina, Chapel Hill; and the Departments of Pathology (R.P.) and Otorhinolaryngology (U.P.), University of Malaya, Kuala Lumpur, Malaysia.

Address reprint requests to Dr. Raab-Traub at the Lineberger Comprehensive cancer Center, CB#7295, University of North Carolina, Chapel Hill, NC 27599-7295.

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Epstein–Barr Virus and Nasopharyngeal Cancer
Meisler A.I., Schuster V., Pukrop T., Raab-Traub N.
Extract | Full Text  
N Engl J Med 1996; 334:122-123, Jan 11, 1996. Correspondence

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