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Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma.
N Engl J Med. 1995 Sep 14; 333(11):693-8.NEJM

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 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.

Authors+Show Affiliations

Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill 27599-7295, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7637746

Citation

Pathmanathan, R, et al. "Clonal Proliferations of Cells Infected With Epstein-Barr Virus in Preinvasive Lesions Related to Nasopharyngeal Carcinoma." The New England Journal of Medicine, vol. 333, no. 11, 1995, pp. 693-8.
Pathmanathan R, Prasad U, Sadler R, et al. Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma. N Engl J Med. 1995;333(11):693-8.
Pathmanathan, R., Prasad, U., Sadler, R., Flynn, K., & Raab-Traub, N. (1995). Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma. The New England Journal of Medicine, 333(11), 693-8.
Pathmanathan R, et al. Clonal Proliferations of Cells Infected With Epstein-Barr Virus in Preinvasive Lesions Related to Nasopharyngeal Carcinoma. N Engl J Med. 1995 Sep 14;333(11):693-8. PubMed PMID: 7637746.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clonal proliferations of cells infected with Epstein-Barr virus in preinvasive lesions related to nasopharyngeal carcinoma. AU - Pathmanathan,R, AU - Prasad,U, AU - Sadler,R, AU - Flynn,K, AU - Raab-Traub,N, PY - 1995/9/14/pubmed PY - 1995/9/14/medline PY - 1995/9/14/entrez SP - 693 EP - 8 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 333 IS - 11 N2 - 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. SN - 0028-4793 UR - https://www.unboundmedicine.com/medline/citation/7637746/Clonal_proliferations_of_cells_infected_with_Epstein_Barr_virus_in_preinvasive_lesions_related_to_nasopharyngeal_carcinoma_ L2 - http://www.nejm.org/doi/full/10.1056/NEJM199509143331103?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -