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 p atients with nasopharyngeal carcinoma. To determine whether EBV infect ion 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 i n situ, Preinvasive lesions were found in 11 samples, which were teste d for the presence of EBV. Methods. EBV infection was detected with in situ hybridization for EBV-encoded RNAs (EBERs) and by immunohistoche mical staining for latent membrane protein 1 (LMP-1). The larger sampl es were also tested for the EBV genome with the use of Southern blotti ng. The expression of specific EBV RNAs was determined by the amplific ation 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 sa mples 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 an tigen 1, LMP-1, LMP-2A, and the BamHI-A fragment, was detected in most of the samples. Viral proteins characteristic of lytic lesions were n ot detected. Conclusions. Preinvasive lesions of the nasopharynx are i nfected with EBV. The EBV DNA is clonal, indicating that the lesions r epresent 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 cont ain EBV RNAs that are characteristic of latent infection but not the v iral proteins that are characteristic of lytic infection. The detectio n of the EBV-transforming gene, LMP-1, in all the neoplastic cells sug gests that its expression is essential for preinvasive epithelial prol iferations associated with nasopharyngeal carcinoma.