Epstein-Barr virus and childhood Hodgkin's disease in Honduras and the United States

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.

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Epstein-Barr virus and childhood Hodgkin's disease in Honduras and the United States

Blood ◽

10.1182/blood.v81.2.462.462 ◽

1993 ◽

Vol 81 (2) ◽

pp. 462-467 ◽

Cited By ~ 144

Author(s):

RF Ambinder ◽

PJ Browning ◽

I Lorenzana ◽

BG Leventhal ◽

H Cosenza ◽

...

Keyword(s):

United States ◽

Hodgkin's Disease ◽

Epstein Barr Virus ◽

Hodgkin’S Disease ◽

The United States ◽

Mixed Cellularity ◽

Detection Techniques ◽

Barr Virus ◽

Epstein Barr ◽

Initial Peak

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.

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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 ◽

10.1182/blood.v83.6.1595.bloodjournal8361595 ◽

1994 ◽

Vol 83 (6) ◽

pp. 1595-1602 ◽

Cited By ~ 1

Author(s):

ML Gulley ◽

PA Eagan ◽

L Quintanilla-Martinez ◽

AL Picado ◽

BN Smir ◽

...

Keyword(s):

Hodgkin's Disease ◽

Odds Ratio ◽

Epstein Barr Virus ◽

Hodgkin’S Disease ◽

Viral Dna ◽

Mixed Cellularity ◽

Hispanic Ethnicity ◽

Barr Virus ◽

Ebv Dna ◽

Epstein Barr

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.

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Association of Epstein-Barr virus genome with mixed cellularity and cellular phase nodular sclerosis Hodgkin's disease subtypes

Annals of Oncology ◽

10.1093/oxfordjournals.annonc.a058187 ◽

1992 ◽

Vol 3 (4) ◽

pp. 307-310 ◽

Cited By ~ 15

Author(s):

M. Boiocchi ◽

V. de Re ◽

R. Dolcetti ◽

A. Carbone ◽

A. Scarpa ◽

...

Keyword(s):

Hodgkin's Disease ◽

Epstein Barr Virus ◽

Hodgkin’S Disease ◽

Virus Genome ◽

Mixed Cellularity ◽

Barr Virus ◽

Nodular Sclerosis ◽

Disease Subtypes ◽

Epstein Barr

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Presence of Epstein-Barr virus and strain type assignment in Argentine childhood Hodgkin's disease

Blood ◽

10.1182/blood.v86.10.3922.bloodjournal86103922 ◽

1995 ◽

Vol 86 (10) ◽

pp. 3922-3929 ◽

Cited By ~ 29

Author(s):

MV Preciado ◽

E De Matteo ◽

B Diez ◽

J Menarguez ◽

S Grinstein

Keyword(s):

Hodgkin's Disease ◽

Epstein Barr Virus ◽

Polymerase Chain Reaction Amplification ◽

Hodgkin’S Disease ◽

Nuclear Antigen ◽

Mixed Cellularity ◽

Barr Virus ◽

Type Assignment ◽

Epstein Barr ◽

Age Range

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.

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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 ◽

10.1182/blood.v83.6.1595.1595 ◽

1994 ◽

Vol 83 (6) ◽

pp. 1595-1602 ◽

Cited By ~ 103

Author(s):

ML Gulley ◽

PA Eagan ◽

L Quintanilla-Martinez ◽

AL Picado ◽

BN Smir ◽

...

Keyword(s):

Hodgkin's Disease ◽

Odds Ratio ◽

Epstein Barr Virus ◽

Hodgkin’S Disease ◽

Viral Dna ◽

Mixed Cellularity ◽

Hispanic Ethnicity ◽

Barr Virus ◽

Ebv Dna ◽

Epstein Barr

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.

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