scholarly journals High expression of the bcl-x gene in Reed-Sternberg cells of Hodgkin's disease

Blood ◽  
1995 ◽  
Vol 85 (10) ◽  
pp. 2671-2674 ◽  
Author(s):  
D Schlaifer ◽  
M March ◽  
S Krajewski ◽  
G Laurent ◽  
J Pris ◽  
...  
Keyword(s):  
Hodgkin's Disease ◽  
Plasma Cells ◽  
Hodgkin’S Disease ◽  
Protein A ◽  
Mixed Cellularity ◽  
Barr Virus ◽  
X Gene ◽  
Epstein Barr ◽  
Apoptosis Regulation

The expression of bcl-x protein, a bcl-2-related protein present in cortical thymocytes, activated lymphocytes, and plasma cells of reactive lymph nodes, was investigated in 44 cases of Hodgkin's disease (HD) in parallel with bcl-2 and Epstein-Barr virus (EBV) status. Eighty-six percent of the cases were positive for bcl-x, among them 27% with a strong signal in more than 75% of the Reed-Sternberg cells. Positivity for bcl-x was found in, respectively, 100% and 92% of the nodular sclerosis and mixed cellularity subtypes, although 4 cases of lymphocyte predominance subtype were negative. This finding was in contrast with the weaker positivity for bcl-2 staining in 44% of the cases. EBV small RNAs were detected in 43% of the cases by using in situ hybridization. Of interest, 100% of the EBV-positive samples were positive for bcl-x, whereas only 38% of these cases were bcl-2 positive. Our findings show that the bcl-x gene expression is high in HD, suggesting that bcl-x may have a role in the pathogenesis of at least some cases of HD via apoptosis regulation.

scholarly journals Demonstration of monoclonal EBV genomes in Hodgkin's disease and Ki-1- positive anaplastic large cell lymphoma by combined Southern blot and in situ hybridization [see comments]

Blood ◽  
1989 ◽  
Vol 74 (2) ◽  
pp. 810-816 ◽  
Author(s):  
I Anagnostopoulos ◽  
H Herbst ◽  
G Niedobitek ◽  
H Stein
Keyword(s):  
In Situ Hybridization ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Viral Genomes ◽  
Barr Virus ◽  
Infected Cells ◽  
Epstein Barr ◽  
Distinct Morphology

Abstract Forty-two cases of Hodgkin's disease (HD) and 22 cases of Ki-1-positive anaplastic large cell (Ki-1 + ALC) lymphoma were examined by Southern blotting for the presence of Epstein-Barr virus (EBV) DNA. Seven cases of HD and one case of Ki-1 + ALC lymphoma scored positive with a probe specific for the internal repetitive region of the EBV genome. Subsequently, these viral genomes could be demonstrated to be monoclonal in origin using an EBV terminal region DNA probe. In situ hybridization revealed that in two HD cases, the EBV infected cells had the distinct morphology of Hodgkin and Reed-Sternberg cells, thus suggesting a direct pathoetiological relationship between EBV and some cases of HD.

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 ◽  
...  
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.

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

Blood ◽  
1995 ◽  
Vol 86 (10) ◽  
pp. 3922-3929 ◽  
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.

scholarly journals In situ demonstration of Epstein-Barr virus small RNAs (EBER 1) in acquired immunodeficiency syndrome-related lymphomas: correlation with tumor morphology and primary site

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 619-624 ◽  
Author(s):  
SJ Hamilton-Dutoit ◽  
M Raphael ◽  
J Audouin ◽  
J Diebold ◽  
I Lisse ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Hodgkin's Disease ◽  
Epstein Barr Virus ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Barr Virus ◽  
Acquired Immunodeficiency ◽  
Epstein Barr ◽  
Immunodeficiency Syndrome

Abstract Some acquired immunodeficiency syndrome (AIDS)-related lymphomas (ARLs) are infected with Epstein-Barr virus (EBV), although the frequency and importance of this association is disputed. Using paraffin section RNA in situ hybridization (ISH) with digoxigenin-labeled riboprobes, we screened 16 central nervous system (CNS) non-Hodgkin's lymphomas (NHLs), 101 systemic NHLs, and 11 Hodgkin's disease cases arising in human immunodeficiency virus-seropositive individuals for EBV-encoded small RNA (EBER 1) expression, an EBV gene product transcribed in abundance during latent infection. Tumor cells contained EBV in 85 of 128 ARLs (66%), but infection rates differed with lymphoma type. EBER 1 was expressed in tumor cells in 11 of 11 Hodgkin's disease cases (100%), 15 of 16 CNS NHLs (94%), and 46 of 60 systemic immunoblast- rich/large-cell lymphomas (77%), but in only 12 of 35 Burkitt-type (small noncleaved cell) (34%) and 1 of 6 monomorphic centroblastic (diffuse large noncleaved cell) (17%) lymphomas. In most EBV-positive ARLs, all recognizable viable tumor cells expressed EBER 1. We conclude that (1) EBV infects tumor cells in all AIDS-related Hodgkin's disease cases, in virtually all primary CNS ARLs, and in most systemic immunoblast-rich/large-cell ARLs; (2) only a minority of Burkitt-type and monomorphic centroblastic lymphomas are associated with EBV; and (3) EBER-ISH is ideal for the histopathologic detection of latent EBV in routine tissue specimens.

scholarly journals In situ demonstration of Epstein-Barr virus small RNAs (EBER 1) in acquired immunodeficiency syndrome-related lymphomas: correlation with tumor morphology and primary site

Blood ◽  
1993 ◽  
Vol 82 (2) ◽  
pp. 619-624 ◽  
Author(s):  
SJ Hamilton-Dutoit ◽  
M Raphael ◽  
J Audouin ◽  
J Diebold ◽  
I Lisse ◽  
...  
Keyword(s):  
Tumor Cells ◽  
Hodgkin's Disease ◽  
Epstein Barr Virus ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Barr Virus ◽  
Acquired Immunodeficiency ◽  
Epstein Barr ◽  
Immunodeficiency Syndrome

Some acquired immunodeficiency syndrome (AIDS)-related lymphomas (ARLs) are infected with Epstein-Barr virus (EBV), although the frequency and importance of this association is disputed. Using paraffin section RNA in situ hybridization (ISH) with digoxigenin-labeled riboprobes, we screened 16 central nervous system (CNS) non-Hodgkin's lymphomas (NHLs), 101 systemic NHLs, and 11 Hodgkin's disease cases arising in human immunodeficiency virus-seropositive individuals for EBV-encoded small RNA (EBER 1) expression, an EBV gene product transcribed in abundance during latent infection. Tumor cells contained EBV in 85 of 128 ARLs (66%), but infection rates differed with lymphoma type. EBER 1 was expressed in tumor cells in 11 of 11 Hodgkin's disease cases (100%), 15 of 16 CNS NHLs (94%), and 46 of 60 systemic immunoblast- rich/large-cell lymphomas (77%), but in only 12 of 35 Burkitt-type (small noncleaved cell) (34%) and 1 of 6 monomorphic centroblastic (diffuse large noncleaved cell) (17%) lymphomas. In most EBV-positive ARLs, all recognizable viable tumor cells expressed EBER 1. We conclude that (1) EBV infects tumor cells in all AIDS-related Hodgkin's disease cases, in virtually all primary CNS ARLs, and in most systemic immunoblast-rich/large-cell ARLs; (2) only a minority of Burkitt-type and monomorphic centroblastic lymphomas are associated with EBV; and (3) EBER-ISH is ideal for the histopathologic detection of latent EBV in routine tissue specimens.

scholarly journals Distribution and phenotype of Epstein-Barr virus-harboring cells in Hodgkin's disease

Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 484-491 ◽  
Author(s):  
H Herbst ◽  
E Steinbrecher ◽  
G Niedobitek ◽  
LS Young ◽  
L Brooks ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Hodgkin's Disease ◽  
Epstein Barr Virus ◽  
Hodgkin’S Disease ◽  
Lymphoid Cells ◽  
Small Cells ◽  
Barr Virus ◽  
Epstein Barr

Distribution and phenotype of Epstein-Barr virus (EBV)-harboring cells were determined in Hodgkin's disease (HD) biopsies by in situ hybridization with [35S]-labeled RNA probes specific for the small EBV- encoded nuclear RNAs, EBER1 and EBER2, in some instances preceded by immunohistology for CD20, CD30, CD45RO, and CD68 antigens, the T-cell receptor beta-chain, and latent membrane antigen (LMP) of EBV. Twenty- three of 46 HD cases displayed EBER transcripts in all Hodgkin and Reed- Sternberg (H-RS) cells, and 18 of these cases showed LMP expression exclusively in neoplastic cells. EBER+ small reactive cells were present in 39 cases in low numbers, and in three cases in abundance. Thus, presence of H-RS cells with or without LMP expression was not accompanied by an unrestricted proliferation of reactive EBER+/LMP- lymphoid cells in the majority of HD patients. Simultaneous in situ hybridization with [35S]-labeled immunoglobulin light chain (IgLC) gene probes and nonisotopically labeled EBER probe showed a phenotype of mature B lymphocytes and a polyclonal composition for a large proportion of the EBER+ small cells. However, in contrast to noninfected cells, CD20 expression was not detectable in many of these cells, which may indicate downregulation of certain differentiation antigens in latently EBV-infected small lymphoid cells in vivo.

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 ◽  
...  
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.

scholarly journals Distribution and phenotype of Epstein-Barr virus-harboring cells in Hodgkin's disease

Blood ◽  
1992 ◽  
Vol 80 (2) ◽  
pp. 484-491 ◽  
Author(s):  
H Herbst ◽  
E Steinbrecher ◽  
G Niedobitek ◽  
LS Young ◽  
L Brooks ◽  
...  
Keyword(s):  
In Situ Hybridization ◽  
Hodgkin's Disease ◽  
Epstein Barr Virus ◽  
Hodgkin’S Disease ◽  
Lymphoid Cells ◽  
Small Cells ◽  
Barr Virus ◽  
Epstein Barr

Abstract Distribution and phenotype of Epstein-Barr virus (EBV)-harboring cells were determined in Hodgkin's disease (HD) biopsies by in situ hybridization with [35S]-labeled RNA probes specific for the small EBV- encoded nuclear RNAs, EBER1 and EBER2, in some instances preceded by immunohistology for CD20, CD30, CD45RO, and CD68 antigens, the T-cell receptor beta-chain, and latent membrane antigen (LMP) of EBV. Twenty- three of 46 HD cases displayed EBER transcripts in all Hodgkin and Reed- Sternberg (H-RS) cells, and 18 of these cases showed LMP expression exclusively in neoplastic cells. EBER+ small reactive cells were present in 39 cases in low numbers, and in three cases in abundance. Thus, presence of H-RS cells with or without LMP expression was not accompanied by an unrestricted proliferation of reactive EBER+/LMP- lymphoid cells in the majority of HD patients. Simultaneous in situ hybridization with [35S]-labeled immunoglobulin light chain (IgLC) gene probes and nonisotopically labeled EBER probe showed a phenotype of mature B lymphocytes and a polyclonal composition for a large proportion of the EBER+ small cells. However, in contrast to noninfected cells, CD20 expression was not detectable in many of these cells, which may indicate downregulation of certain differentiation antigens in latently EBV-infected small lymphoid cells in vivo.

scholarly journals Frequent expression of the cell death-inducing gene Bax in Reed- Sternberg cells of Hodgkin's disease

Blood ◽  
1996 ◽  
Vol 87 (6) ◽  
pp. 2470-2475 ◽  
Author(s):  
F Rigal-Huguet ◽  
J Gopas ◽  
I Prinsloo ◽  
J Pris ◽  
G Delsol ◽  
...  
Keyword(s):  
Cell Death ◽  
Hodgkin's Disease ◽  
Epstein Barr Virus ◽  
Hodgkin’S Disease ◽  
Potential Explanation ◽  
Barr Virus ◽  
Strong Signal ◽  
A Cell ◽  
Epstein Barr

The expression of a cell death-inducing gene, Bax, was investigated in 52 cases of Hodgkin's disease in parallel with Epstein-Barr virus and was compared with the immunodetection of other apoptosis-regulating proteins, Mcl-1, Bcl-2, and Bcl-x. Bax immunostaining was found in 92% of the cases, among them 28% with a strong signal in more than 75% of the Reed-Sternberg cells. Mcl-1 was positive in 80% of the cases, whereas Bcl-2 and Bcl-x were found in 53% and 88% of the cases, respectively. Of 48 (89%) Bax-positive tumors, 43 were found to express apoptosis-inhibiting proteins such as Mcl-1 or Bcl-2. With the exception of 1 case, all Bax-positive tumors also expressed either Bcl- 2, Bcl-x, Mcl-1, or combinations of these anti-apoptotic proteins. No correlation was found between Bax expression and the presence of apoptotic cells as detected by morphology and the in situ 3′ OH-DNA end- labeling technique. Our findings show that the apoptosis-inducing gene Bax expression is frequently expressed in Hodgkin's disease, providing a potential explanation for the good chemoresponses generally obtained for patients with this neoplastic disorder.

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