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]

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.

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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 ◽

10.1182/blood.v74.2.810.bloodjournal742810 ◽

1989 ◽

Vol 74 (2) ◽

pp. 810-816 ◽

Cited By ~ 2

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

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.

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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 ◽

10.1182/blood.v82.2.619.619 ◽

1993 ◽

Vol 82 (2) ◽

pp. 619-624 ◽

Cited By ~ 182

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.

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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 ◽

10.1182/blood.v82.2.619.bloodjournal822619 ◽

1993 ◽

Vol 82 (2) ◽

pp. 619-624 ◽

Cited By ~ 5

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.

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

Blood ◽

10.1182/blood.v80.2.484.bloodjournal802484 ◽

1992 ◽

Vol 80 (2) ◽

pp. 484-491 ◽

Cited By ~ 1

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.

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

Blood ◽

10.1182/blood.v80.2.484.484 ◽

1992 ◽

Vol 80 (2) ◽

pp. 484-491 ◽

Cited By ~ 126

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.

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Demonstration of Epstein-Barr Virus Genome in Neoplastic Cells of Hodgkin's Disease by in Situ Hybridization, in Paraffin-Embedded Tissue using Biotinylated Probes

Pathology - Research and Practice ◽

10.1016/s0344-0338(11)81209-4 ◽

1992 ◽

Vol 188 (3) ◽

pp. 310-313 ◽

Cited By ~ 13

Author(s):

A. Karameris ◽

P. Kanavaros

Keyword(s):

In Situ Hybridization ◽

Hodgkin's Disease ◽

Epstein Barr Virus ◽

Hodgkin’S Disease ◽

Virus Genome ◽

Neoplastic Cells ◽

Barr Virus ◽

Epstein Barr ◽

Biotinylated Probes

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

Blood ◽

10.1182/blood.v85.10.2671.bloodjournal85102671 ◽

1995 ◽

Vol 85 (10) ◽

pp. 2671-2674 ◽

Cited By ~ 45

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.

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