Epstein-Barr virus nuclear antigen-2 detection and typing in immunocompromised children correlated with lymphoproliferative disorder biopsy findings

Epstein-Barr virus (EBV), the causative agent of infectious mononucleosis, plays a significant role as a cofactor in the process of tumorigenesis, and has consistently been associated with a variety of malignancies especially in immunocompromised patients. Forty-four children and adolescents (21 liver transplant patients, 7 heart transplant, 5 AIDS, 3 autoimmune hepatitis, 2 nephritic syndromes, 2 medullar aplasia, 2 primary immunodeficiency disorder patients, 1 thrombocytopenic purpura and 1 systemic lupus erythematosus) presenting with chronic active EBV infection (VCA-IgM persistently positive; VCA-IgG > 20 AU/mL and positive IgG _ EBNA) had peripheral blood samples obtained during clinically characterized EBV reactivation episodes. DNA samples were amplified in order to detect and type EBV on the basis of the EBNA-2 sequence (EBNA2 protein is essential for EBV-driven immortalization of B lymphocytes). Although we have found a predominance of type 1 EBNA-2 virus (33/44; 75 percent), 10 patients (22.73 percent) carried type 2 EBNA-2, and one liver transplant patient (2.27 percent) a mixture of the two types, the higher proportion of type 2 EBV, as well as the finding of one patient bearing the two types is in agreement with other reports held on lymphoproliferative disorder (LPD) patients, which analyzed tumor biopsies. We conclude that EBNA-2 detection and typing can be performed in peripheral blood samples, and the high prevalence of type 2 in our casuistic indicates that this population is actually at risk of developing LPD, and should be monitored.

Polymerase chain reaction genotyping of Epstein-Barr virus in scraping samples of the tongue lateral border in HIV-1 seropositive patients

The Epstein-Barr virus (EBV) is the etiological agent of oral hairy leukoplakia (OHL), an oral lesion with important diagnostic and prognostic value in acquired immunodeficiency disease syndrome. The two EBV genotypes, EBV-1 and EBV-2, can be distinguished by divergent gene sequences encoding the EBNA-2, 3A, 3B, and 3C proteins. The purpose of this study was to identify the EBV genotype prevalent in 53 samples of scrapings from the lateral border of the tongue of HIV-1 seropositive patients, with and without OHL, and to correlate the genotypes with presence of clinical or subclinical OHL with the clinic data collected. EBV-1 and EBV-2 were identified through PCR and Nested-PCR based on sequence differences of the EBNA-2 gene. EBV-1 was identified in the 31 samples (15 without OHL, 7 with clinical OHL and 9 with subclinical OHL), EBV-2 in 12 samples (10 without OHL, 1 with clinical and 1 subclinical OHL), and a mixed infection in 10 samples (2 without OHL, 3 with clinical and 5 with subclinical OHL). The presence of EBV-1 was higher in women, but a significant statistical result relating one the EBV genotypes to the development of OHL was not found. We conclude that the oral epithelium in HIV-1 seropositive patients can be infected by EBV-1, EBV-2 or by a mixed viral population.

Expression of LMP-1、EBNA-2 in the Follicular Epithelium Neoplasm of the Thyroid / 医学研究杂志

0.05);LMP-1 and EBNA-2 in papillary thyroid carcinoma had no correlation.Conclusion Some thyroid papillary carcinomas may be related to EB virus infection,the relationship has yet to be further studied.

Clinical Significance of Epstein-Barr Virus Expression in Breast Cancer / 한국유방암학회지

PURPOSE: Epstein-Barr Virus (EBV) is well understood as an oncogenic virus in human tumors. Its association with breast cancers has been reported but is still in controversy. So we have examined the expression of EBV in breast cancers and evaluated the relationship between the well-known prognositc factors of breast cancer and EBV expression. METHODS: A retrospective study was conducted with patients who had been re-evaluated to confirm the diagnosis based on immunohistochemical analysis with EBNA-2 expression, between January 1991 and December 2002. The cases were assigned to the positive lesion that displayed 10% or more of immunoreactive cells. RESULTS: The expressions of EBNA-2(Ebstein Barr virus nuclear antigen - 2) were noted in 26 (21.1%) out of 123 cases of breast cancer patients and 4 (20%) out of 20 cases in a control group of benign tumors. The expression of EBV in breast cancers and that of a control group were not different significantly. But, the correlation between the expression of EBNA-2 and ER status was noted statistically significant (P=0.040). CONCLUSION: Judging from the results of our study, EBV infection detected in breast cancer seems to be latent and the association of EBV to breast cancer is less likely related.

Detection and Subtyping of Epstein-Barr Virus in Gastrointestinal Adenocarcinomas and Malignant Lymphomas

Epstein-Barr virus (EBV) has been linked to a spectrum of neoplastic conditions, including Burkitt's lymphoma, nasopharyngeal carcinoma, Hodgkin's disease, lymphoepithelioma-like carcinomas and malignant lymphomas in immunocompromised state. To determine the prevalence and the subtype of EBV in gatrointestinal malignancies, fifty cases of adenocarcinomas and seventeen cases of malignant lymphomas were analyzed by EBERs in situ hybridization and polymerase chain reaction using primers for EBNA-1, EBNA-2A and EBNA-2B, on the paraffin sections. In addition, immunohistochemical stain for p53 protein was performed to investigate the potential role of EBV infection on tumor suppressor gene, p53, during tumorigenesis. EBER was detected in 6 of 26 gastric adenocarcinomas, 2 of 24 colon adenocarcinomas, and 8 of 17 malignant lymphomas. EBER was more prevalent in malignant lymphoma arising in the intestine (6/6) than in the stomach (2/11), and was detected in both B and T cell phenotypes. EBNA-1 was positive in 11 of 16 EBER positive cases and the subtyping was possible in 8; both type 1 and 2 were detected in gastric cancers, whereas only type 2 was found in intestinal neoplasms. In adenocarcinomas the high rate of p53 protein overexpression was found in both EBER positive (8/8) and negative cases (32/42), whereas the positive rate was higher in EBER positive cases (7/8) than in EBER negative cases (4/9) of malignant lymphomas. From the results, it can be concluded that EBV infection and the p53 tumor suppressor gene are independently associated in a significant portion of the gastrointestinal malignancies, but the mechanism of action remains to be elucidated.