scholarly journals Epstein-Barr virus DNA is abundant and monoclonal in the Reed-Sternberg cells of Hodgkin's disease: association with mixed cellularity subtype and Hispanic American ethnicity

Blood ◽  
1994 ◽  
Vol 83 (6) ◽  
pp. 1595-1602 ◽  
Author(s):  
ML Gulley ◽  
PA Eagan ◽  
L Quintanilla-Martinez ◽  
AL Picado ◽  
BN Smir ◽  
...  

One hundred twenty-five cases of Hodgkin's disease from the United States (79), Mexico City (31), and Costa Rica (15) were analyzed for the presence of Epstein-Barr virus (EBV) by in situ hybridization to EBER1 transcripts. EBV was more frequently detected in the Reed- Sternberg (RS) cells of mixed cellularity Hodgkin's disease (37 of 48 [77%]) compared with the nodular sclerosis subtype (19 of 71 [27%], P < .001). The presence of EBV was also associated with Hispanic ethnicity (P < .001). In a multivariate analysis, patient age, gender, and geographic location were less predictive of EBV positivity than were mixed cellularity histology (odds ratio = 8.3) and Hispanic ethnicity (odds ratio = 4.3). Southern blot analysis of EBV terminal repeat fragments using the Xho1a probe showed that the viral DNA was monoclonal in 17 of 17 cases having EBER1-positive RS cells. By comparison, EBV DNA was not detected by Southern analysis in 20 cases lacking EBER1 in RS cells, even when occasional background lymphocytes expressed EBER1. Because clonal viral DNA was so readily detected in EBER1-positive cases, the EBV genome is probably amplified at least 50- fold in the infected RS cells. Monoclonality of EBV DNA implies that the RS cells were infected before malignant transformation.

Blood ◽  
1994 ◽  
Vol 83 (6) ◽  
pp. 1595-1602 ◽  
Author(s):  
ML Gulley ◽  
PA Eagan ◽  
L Quintanilla-Martinez ◽  
AL Picado ◽  
BN Smir ◽  
...  

Abstract One hundred twenty-five cases of Hodgkin's disease from the United States (79), Mexico City (31), and Costa Rica (15) were analyzed for the presence of Epstein-Barr virus (EBV) by in situ hybridization to EBER1 transcripts. EBV was more frequently detected in the Reed- Sternberg (RS) cells of mixed cellularity Hodgkin's disease (37 of 48 [77%]) compared with the nodular sclerosis subtype (19 of 71 [27%], P < .001). The presence of EBV was also associated with Hispanic ethnicity (P < .001). In a multivariate analysis, patient age, gender, and geographic location were less predictive of EBV positivity than were mixed cellularity histology (odds ratio = 8.3) and Hispanic ethnicity (odds ratio = 4.3). Southern blot analysis of EBV terminal repeat fragments using the Xho1a probe showed that the viral DNA was monoclonal in 17 of 17 cases having EBER1-positive RS cells. By comparison, EBV DNA was not detected by Southern analysis in 20 cases lacking EBER1 in RS cells, even when occasional background lymphocytes expressed EBER1. Because clonal viral DNA was so readily detected in EBER1-positive cases, the EBV genome is probably amplified at least 50- fold in the infected RS cells. Monoclonality of EBV DNA implies that the RS cells were infected before malignant transformation.


Blood ◽  
1995 ◽  
Vol 86 (10) ◽  
pp. 3922-3929 ◽  
Author(s):  
MV Preciado ◽  
E De Matteo ◽  
B Diez ◽  
J Menarguez ◽  
S Grinstein

Epstein-Barr virus (EBV) has been implicated in the etiology of a large number of malignancies. Most recently several studies have linked EBV to Hodgkin's disease. In this report, formalin-fixed, paraffin-embedded tissues were collected retrospectively from 41 children with Hodgkin's disease treated at our hospital. Lymph node biopsies were examined for the presence of two virus-encoded latent proteins: latent membrane protein (LMP) and Epstein-Barr nuclear antigen-2 (EBNA-2), in Reed- Sternberg (RS) and Hodgkin (H) cells, by peroxidase immunolabeling. Nonisotopic Epstein-Barr encoded RNAs (EBERs) in situ hybridization was also performed and positive labeling in malignant cells was detected. Twenty specimens were EBER+/LMP+, 2 were EBER+/LMP-, and 19 were EBER- /LMP-. However, none of the 41 cases expressed EBNA-2. Twenty-two of 41 (54%) cases were EBV positive including 2 of 6 with lymphocyte predominance, 19 of 25 with mixed cellularity, 0 of 9 with nodular sclerosis, and 1 of 1 with lymphocyte depletion. In the age range of 2 to 6 years, 14 of 17 (82%) samples were EBV-positive, whereas only 8 of 24 (33%) samples from the age range of 7 to 15 years contained EBV. (P = .004), a two-tailed Fisher's test). In 17 samples, polymerase chain reaction amplification was performed using strain specific primers for exon sequences of the EBNA-3C gene of EBV. From 12 positive samples, 8 contained EBV-A and 4 EBV-B. These results support the hypothesis that EBV contributes to the pathogenesis of pediatric Hodgkin's disease, particularly in mixed cellularity Hodgkin's disease and in the younger group.


2006 ◽  
Vol 124 (3) ◽  
pp. 154-157 ◽  
Author(s):  
Juliane Garcez Musacchio ◽  
Maria da Glória da Costa Carvalho ◽  
José Carlos Oliveira de Morais ◽  
Nathalie Henriques Silva ◽  
Adriana Scheliga ◽  
...  

CONTEXT AND OBJECTIVE: Free circulating Epstein-Barr virus (EBV) DNA is often present in the plasma of Hodgkin’s disease patients. The aim here was to evaluate the prevalence of this finding, its correlation with the immunohistochemical expression of LMP-1 (latent membrane protein 1) and the influence of other clinical factors. DESIGN AND SETTING: Prospective study in two public tertiary institutions: Hematology Service, Universidade Federal do Rio de Janeiro, and Oncology Service, Instituto Nacional do Câncer, Rio de Janeiro. METHODS: A cohort of 30 patients with newly diagnosed Hodgkin’s disease was studied. The control group consisted of 13 healthy adult volunteers. EBV DNA was determined by conventional polymerase chain reaction (PCR). RESULTS: The median age was 28 years, and 16 patients were women. Advanced disease was present in 19 patients, and six were HIV-positive. EBV DNA was present in the plasma of 13 patients and one control (43% versus 8%, p = 0.03). EBV DNA prevalence was higher in HIV-positive patients (100% versus 29%, p = 0.0007) and those with advanced disease (63% versus 9%, p = 0.006). Among HIV-negative patients alone, EBV DNA prevalence remained higher in those with advanced disease. EBV DNA was found in 10/11 patients with LMP-1 expression in the lymph nodes, and in 3/19 without LMP-1 expression (kappa coefficient = 0.72). CONCLUSION: EBV DNA was present in 91% of patients with EBV-associated Hodgkin’s disease, and in all patients with HIV-associated Hodgkin’s disease. EBV DNA prevalence was higher in patients with advanced disease, irrespective of HIV status.


Blood ◽  
1993 ◽  
Vol 81 (2) ◽  
pp. 462-467 ◽  
Author(s):  
RF Ambinder ◽  
PJ Browning ◽  
I Lorenzana ◽  
BG Leventhal ◽  
H Cosenza ◽  
...  

Abstract In industrialized populations, Hodgkin's disease (HD) has an initial peak in young adulthood, whereas in economically developing populations the initial peak occurs in childhood. This pattern resembles that of infection with poliovirus and suggests an infectious cofactor in the etiology. Serologic studies have linked Epstein-Barr virus (EBV) to young adult and adult HD, and viral nucleic acids and antigens have been detected in a subset of Hodgkin's tumor specimens. To investigate the association of childhood HD with EBV we studied tumor specimens from 11 children treated in Honduras and 25 children treated in the United States using in situ hybridization and antigen detection techniques. Among the patients from Honduras, tumor specimens from all cases were EBV positive. Among the patients from the United States, tumor specimens from six of seven patients with mixed cellularity histology, 2 of 15 with nodular sclerosis histology, and neither of two patients with lymphocyte-predominant histologies were EBV positive. These findings support the hypothesis that EBV contributes to the pathogenesis of HD in children, particularly in mixed cellularity HD, and raises the possibility that there are important geographic, racial, or ethnic factors in the EBV association with HD.


Blood ◽  
1993 ◽  
Vol 81 (2) ◽  
pp. 462-467 ◽  
Author(s):  
RF Ambinder ◽  
PJ Browning ◽  
I Lorenzana ◽  
BG Leventhal ◽  
H Cosenza ◽  
...  

In industrialized populations, Hodgkin's disease (HD) has an initial peak in young adulthood, whereas in economically developing populations the initial peak occurs in childhood. This pattern resembles that of infection with poliovirus and suggests an infectious cofactor in the etiology. Serologic studies have linked Epstein-Barr virus (EBV) to young adult and adult HD, and viral nucleic acids and antigens have been detected in a subset of Hodgkin's tumor specimens. To investigate the association of childhood HD with EBV we studied tumor specimens from 11 children treated in Honduras and 25 children treated in the United States using in situ hybridization and antigen detection techniques. Among the patients from Honduras, tumor specimens from all cases were EBV positive. Among the patients from the United States, tumor specimens from six of seven patients with mixed cellularity histology, 2 of 15 with nodular sclerosis histology, and neither of two patients with lymphocyte-predominant histologies were EBV positive. These findings support the hypothesis that EBV contributes to the pathogenesis of HD in children, particularly in mixed cellularity HD, and raises the possibility that there are important geographic, racial, or ethnic factors in the EBV association with HD.


Author(s):  
S.I. Kutukova ◽  
A.B. Chukhlovin ◽  
A.I. Yaremenko ◽  
Yu.V. Ivaskova ◽  
A.Ya. Razumova ◽  
...  

The aim of the study was to assess the prevalence of DNA viruses (HSV I and II, CMV, EBV, HPV6.11, HPV16 and HPV18) in the native oral mucosa of healthy volunteers (n=50; 30 men (60.0%), 20 women (40.0%); 25—74 years, median age — 55.0 years (95% CI 47.60-56.76)). All samples of the normal oral mucosa were detected by real-time PCR to detect viral DNA. The majority of the examined — 76% (33/50) — revealed the DNA: one type of viral DNA in 17 (38.00%) of the examined, a combination of the two types in 14 (28.00%). In the normal oral mucosa, DNA of Epstein-Barr virus was significantly more often detected: 15 (30.00%) (p = 0.0276) and human papilloma viruses 27 (54.00%) (p <0.0001), especially HPV-18 (24 (48.00%)): mono-association in 9 (18.00%) examined and in 7 (14.00%) in combination with EBV DNA (p = 0.0253).


1992 ◽  
Vol 98 (3) ◽  
pp. 319-323 ◽  
Author(s):  
Christian Fellbaum ◽  
Martin-Leo Hansmann ◽  
Hans Niedermeyer ◽  
Irmgard Kraus ◽  
Martti J. Alavaikko ◽  
...  

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