scholarly journals The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells

Blood ◽  
1985 ◽  
Vol 66 (4) ◽  
pp. 848-858 ◽  
Author(s):  
H Stein ◽  
DY Mason ◽  
J Gerdes ◽  
N O'Connor ◽  
J Wainscoat ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Lymphoid Cells ◽  
Cell Phenotype ◽  
Cell Type ◽  
Lymphomatoid Papulosis ◽  
T Cell Lymphomas ◽  
Immunoblastic Lymphadenopathy

Ki-1 is a monoclonal antibody (raised against a Hodgkin's disease- derived cell line) that, in biopsy tissue affected by Hodgkin's disease, reacts selectively with Reed-Sternberg cells. The expression of Ki-1 antigen has been analyzed by immunocytochemical techniques in a wide range of human tissue and cell samples, including fetal tissue, malignant lymphomas (290 cases), and mitogen- and virus-transformed peripheral blood lymphocytes. The antigen was detectable on a variable proportion of cells in all cases of lymphomatoid papulosis and angio- immunoblastic lymphadenopathy and in 28% of the cases of peripheral T cell lymphomas (including lympho-epithelioid lymphomas). It was also expressed (more strongly) on tumor cells in 45 cases of diffuse large- cell lymphoma, most of which had originally been diagnosed as malignant histiocytosis or anaplastic carcinoma, because of their bizarre morphology. However, all of these cases lacked macrophage and epithelial antigens. Thirty-five cases expressed T cell-related antigens (associated in nine cases with the coexpression of B cell- related antigens), seven bore B cell-related antigens alone, and three were devoid of T and B cell markers. DNA hybridization with a JH specific probe showed a germline configuration in 11 cases of T cell phenotype, in two cases lacking T and B cell antigens, and in one case of mixed T/B phenotype, while rearrangement was found in two cases of clear B cell type and in one mixed T/B case. Expression of the Ki-1 antigen could be induced, together with interleukin 2 (IL 2) receptor, on normal lymphoid cells of both T and B cell type by exposure to phytohemagglutinin, human T leukemia viruses, Epstein-Barr virus, or Staphylococcus aureus. The results obtained indicate that Ki-1 antigen is an inducible lymphoid-associated molecule that identifies a group of hitherto poorly characterized normal and neoplastic large lymphoid cells. Tumors comprised solely of these cells show both morphological and immunological similarities to the neoplastic cells in Hodgkin's disease. This suggests that both disorders represent the neoplastic proliferation of activated lymphoid cells of either T cell or, less commonly, B cell origin. Disorders in which only a minority of cells express Ki-1 antigen (lymphomatoid papulosis, angio-immunoblastic lymphadenopathy, and certain T cell lymphomas) probably represent lesions in which only some of the abnormal cells have transformed into an “activation state.” In direct support of this view is the finding that the Ki-1 expression in these lesions is accompanied by the expression of HLA-DR and IL 2 receptors.

scholarly journals The expression of the Hodgkin's disease associated antigen Ki-1 in reactive and neoplastic lymphoid tissue: evidence that Reed-Sternberg cells and histiocytic malignancies are derived from activated lymphoid cells

Blood ◽  
1985 ◽  
Vol 66 (4) ◽  
pp. 848-858 ◽  
Author(s):  
H Stein ◽  
DY Mason ◽  
J Gerdes ◽  
N O'Connor ◽  
J Wainscoat ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Lymphoid Cells ◽  
Cell Phenotype ◽  
Cell Type ◽  
Lymphomatoid Papulosis ◽  
T Cell Lymphomas ◽  
Immunoblastic Lymphadenopathy

Abstract Ki-1 is a monoclonal antibody (raised against a Hodgkin's disease- derived cell line) that, in biopsy tissue affected by Hodgkin's disease, reacts selectively with Reed-Sternberg cells. The expression of Ki-1 antigen has been analyzed by immunocytochemical techniques in a wide range of human tissue and cell samples, including fetal tissue, malignant lymphomas (290 cases), and mitogen- and virus-transformed peripheral blood lymphocytes. The antigen was detectable on a variable proportion of cells in all cases of lymphomatoid papulosis and angio- immunoblastic lymphadenopathy and in 28% of the cases of peripheral T cell lymphomas (including lympho-epithelioid lymphomas). It was also expressed (more strongly) on tumor cells in 45 cases of diffuse large- cell lymphoma, most of which had originally been diagnosed as malignant histiocytosis or anaplastic carcinoma, because of their bizarre morphology. However, all of these cases lacked macrophage and epithelial antigens. Thirty-five cases expressed T cell-related antigens (associated in nine cases with the coexpression of B cell- related antigens), seven bore B cell-related antigens alone, and three were devoid of T and B cell markers. DNA hybridization with a JH specific probe showed a germline configuration in 11 cases of T cell phenotype, in two cases lacking T and B cell antigens, and in one case of mixed T/B phenotype, while rearrangement was found in two cases of clear B cell type and in one mixed T/B case. Expression of the Ki-1 antigen could be induced, together with interleukin 2 (IL 2) receptor, on normal lymphoid cells of both T and B cell type by exposure to phytohemagglutinin, human T leukemia viruses, Epstein-Barr virus, or Staphylococcus aureus. The results obtained indicate that Ki-1 antigen is an inducible lymphoid-associated molecule that identifies a group of hitherto poorly characterized normal and neoplastic large lymphoid cells. Tumors comprised solely of these cells show both morphological and immunological similarities to the neoplastic cells in Hodgkin's disease. This suggests that both disorders represent the neoplastic proliferation of activated lymphoid cells of either T cell or, less commonly, B cell origin. Disorders in which only a minority of cells express Ki-1 antigen (lymphomatoid papulosis, angio-immunoblastic lymphadenopathy, and certain T cell lymphomas) probably represent lesions in which only some of the abnormal cells have transformed into an “activation state.” In direct support of this view is the finding that the Ki-1 expression in these lesions is accompanied by the expression of HLA-DR and IL 2 receptors.

scholarly journals CD30 (Ki-1)-positive malignant lymphomas: clinical, immunophenotypic, histologic, and genetic characteristics and differences with Hodgkin's disease

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2905-2917 ◽  
Author(s):  
DA Filippa ◽  
M Ladanyi ◽  
N Wollner ◽  
DJ Straus ◽  
JP O'Brien ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Bone Marrow Involvement ◽  
Skin Lesions ◽  
Cell Phenotype ◽  
Cell Type ◽  
Null Cell

This study compares the histologic and immunophenotypic features of 71 cases of primary CD30+ diffuse large-cell lymphomas (DLCL) and 128 cases of Hodgkin's disease (HD) and discusses the clinical features of 52 patients with CD30+ DLCL. It includes analysis of sites of involvement, staging, response to treatment, sites and treatment of recurrences, and disease-free and overall survival. Diagnostic immunophenotypic differences were found between CD30+ DLCL and HD. All cases of CD30+ DLCL were positive for one or more common or lineage- specific lymphocyte antigens or for EMA. In contrast, 96.9% of HD cases were negative for CD45, CD45-RO, CD43, and CD20. The four exceptions are discussed. All cases of HD were negative for EMA. In patients with CD30+ DLCL, a T-cell phenotype was found in 60%, a null-cell type in 22%, and a B-cell type in 18% of the cases. The median age of patients with T- and null-cell phenotype was 22 years (range, 4 to 72). Fifty- two percent of them had high-stage (III and IV) disease and 61% had extranodal involvement at presentation, including 25% with skin lesions. Lymph nodes draining the skin lesions became involved in seven of 11 patients. No patient had initial bone marrow involvement. Most patients were treated with chemotherapy, and 83% had a complete remission. Fifty-four percent remain free of disease with a median follow-up of 47 months. Thirteen patients (29%) had one or more recurrences and five of them remain free of disease after salvage therapy, with a median follow-up period of 79 months. The clinical stage did not affect survival, probably as a result of different therapy. The t(2;5) translocation was found in five of 15 patients who had cytogenetic abnormalities. Of the other 10 cases, the translocation was detected by reverse transcriptase-polymerase chain reaction (RT- PCR) in four of five cases studied. All nine cases were of T- or null- cell phenotype. The cases of B-cell CD30+ DLCL had a characteristic immunophenotype. All were negative for EMA. These patients were older and had frequent bone marrow involvement but no skin infiltration by lymphoma. All three patients who were human immunodeficiency virus- positive (HIV+) had lymphomas of B-cell lineage. Detection of the t(2;5) translocation by molecular genetics is a useful and highly specific marker in the differential diagnosis between HD and CD30+ DLCL.

scholarly journals Hodgkin's disease with a B-cell phenotype often shows a VDJ rearrangement and somatic mutations in the VH genes

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 708-715 ◽  
Author(s):  
J Tamaru ◽  
M Hummel ◽  
M Zemlin ◽  
B Kalvelage ◽  
H Stein
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Hodgkin's Disease ◽  
Somatic Mutations ◽  
Hodgkin’S Disease ◽  
Receptor Gene ◽  
High Sensitivity ◽  
Cell Phenotype ◽  
Igh Genes

Abstract The nature of Hodgkin and Reed-Sternberg (HRS) cells remains in question. Immunophenotypic studies favor a relation to the lymphoid lineage with the existence of B- and T-cell types. However, studies on the detection of antigen (Ag) receptor gene rearrangements provided inconsistent results. They concur in that rearranged Ig and T-cell receptor (TCR) genes are not demonstrable in most Hodgkin's disease (HD) cases. To clarify whether this is because of the insensitivity of the method of detection or a real absence of clonal Ig heavy chain (IgH) rearrangements, a polymerase chain reaction (PCR) method with high sensitivity was applied, allowing the detection of less than 50 cells with clonally rearranged IgH genes in a mixture of 100,000 germline or individually rearranged cells. In 67 cases of HD, most of those (67%) with B-Ag+ HRS cells express clonal VDJ rearrangements of the IgH gene. No cases with T-cell Ag+ HRS cells harbored detectable clonal VDJ rearrangements. Of 10 sequenced rearranged IgH genes, the VH segment of six contained considerable somatic mutations. These results suggest that the demonstrated VDJ rearrangements stem from the HRS cells themselves and that the HRS cells of cases with rearranged IgH genes are B-cell related and correspond in their differentiation stage either to naive pregerminal center B cells or (more commonly) to germinal center/postgerminal center-derived memory B cells.

scholarly journals Hodgkin's disease with a B-cell phenotype often shows a VDJ rearrangement and somatic mutations in the VH genes

Blood ◽  
1994 ◽  
Vol 84 (3) ◽  
pp. 708-715 ◽  
Author(s):  
J Tamaru ◽  
M Hummel ◽  
M Zemlin ◽  
B Kalvelage ◽  
H Stein
Keyword(s):  
T Cell ◽  
B Cells ◽  
B Cell ◽  
Hodgkin's Disease ◽  
Somatic Mutations ◽  
Hodgkin’S Disease ◽  
Receptor Gene ◽  
High Sensitivity ◽  
Cell Phenotype ◽  
Igh Genes

The nature of Hodgkin and Reed-Sternberg (HRS) cells remains in question. Immunophenotypic studies favor a relation to the lymphoid lineage with the existence of B- and T-cell types. However, studies on the detection of antigen (Ag) receptor gene rearrangements provided inconsistent results. They concur in that rearranged Ig and T-cell receptor (TCR) genes are not demonstrable in most Hodgkin's disease (HD) cases. To clarify whether this is because of the insensitivity of the method of detection or a real absence of clonal Ig heavy chain (IgH) rearrangements, a polymerase chain reaction (PCR) method with high sensitivity was applied, allowing the detection of less than 50 cells with clonally rearranged IgH genes in a mixture of 100,000 germline or individually rearranged cells. In 67 cases of HD, most of those (67%) with B-Ag+ HRS cells express clonal VDJ rearrangements of the IgH gene. No cases with T-cell Ag+ HRS cells harbored detectable clonal VDJ rearrangements. Of 10 sequenced rearranged IgH genes, the VH segment of six contained considerable somatic mutations. These results suggest that the demonstrated VDJ rearrangements stem from the HRS cells themselves and that the HRS cells of cases with rearranged IgH genes are B-cell related and correspond in their differentiation stage either to naive pregerminal center B cells or (more commonly) to germinal center/postgerminal center-derived memory B cells.

scholarly journals BHRF1, the Epstein-Barr virus (EBV) homologue of the BCL-2 protooncogene, is transcribed in EBV-associated B-cell lymphomas and in reactive lymphocytes

Blood ◽  
1995 ◽  
Vol 86 (5) ◽  
pp. 1893-1902 ◽  
Author(s):  
JJ Oudejans ◽  
AJ van den Brule ◽  
NM Jiwa ◽  
PC de Bruin ◽  
GJ Ossenkoppele ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Lytic Cycle ◽  
B Cell Lymphomas ◽  
Barr Virus ◽  
T Cell Lymphomas ◽  
Epstein Barr ◽  
Reactive Lymphocytes

BHRF1, one of many Epstein-Barr virus (EBV)-encoded proteins, shows strong functional homology to the human bcl-2 proto-oncogene product, a protein involved in the pathogenesis of a subset of B-cell lymphomas, ie, follicle center cell lymphomas (FCCL). We have investigated the presence of possible latent and lytic transcripts of BHRF1 using a reverse transcriptase-polymerase chain reaction (RT-PCR)-based assay in a group of EBV-associated B-cell lymphomas in patients with (N = 5) or without overt immunodeficiency (N = 4), in T-cell lymphomas (N = 9), and in cases of Hodgkin's disease (N = 6). BHRF1 transcription was found consistently in EBV-associated (ie, diffuse EBER 1/2-positive) B- cell lymphomas in patients with or without immune deficiency, whereas in EBV-associated T-cell lymphomas or in EBV-associated Hodgkin's disease, BHRF1 transcription was only detected in two T-cell lymphomas and one case of Hodgkin's disease, which also harbored EBER 1/2- positive reactive cells. Moreover, weak BHRF1 signals were found in two T-cell lymphomas where EBER 1/2 expression was detected mainly in sporadic reactive lymphocytes and in one reactive tonsil with sporadic EBER 1/2-positive lymphocytes. BHRF1 transcripts were found to be generated by the C or W promoter (associated with viral latency) and/or by the H promoter (associated with the virus lytic cycle). In all cases with H promoter-derived BHRF1 transcripts, transcripts encoding ZEBRA were also detected, suggesting a reactivation of the virus lytic cycle. Analysis of other EBV genes revealed transcription of BARFO in all tested EBV-harboring tissues. Transcription of EBNA1 and LMP1 was usually detected, whereas EBNA2 transcription was found exclusively in B-cell lymphomas in immunocompromised patients. These data demonstrate that BHRF1 transcripts are exclusively found in EBV-associated B-cell lymphomas. When BHRF1 transcripts are detected in T-cell lymphomas or in Hodgkin's disease, it is probably due to the presence of reactive EBER 1/2-positive lymphocytes. The consistent transcription of BHRF1 in EBV-associated B-cell lymphomas suggests a possible pathogenic role for this gene product in EBV-positive B-cell lymphomas analogous to bcl-2.

Hodgkin's Disease, Lymphomatoid Papulosis, and Cutaneous T-Cell Lymphoma Derived from a Common T-Cell Clone

1992 ◽  
Vol 326 (17) ◽  
pp. 1115-1122 ◽  
Author(s):  
Thomas H. Davis ◽  
Cynthia C. Morton ◽  
Robert Miller-Cassman ◽  
Steven P. Balk ◽  
Marshall E. Kadin
Keyword(s):  
T Cell ◽  
Hodgkin's Disease ◽  
Cell Lymphoma ◽  
Cell Clone ◽  
Hodgkin’S Disease ◽  
T Cell Lymphoma ◽  
Cutaneous T Cell Lymphoma ◽  
Lymphomatoid Papulosis ◽  
T Cell Clone

scholarly journals HOXC4, HOXC5, and HOXC6 Expression in Non-Hodgkin's Lymphoma: Preferential Expression of the HOXC5 Gene in Primary Cutaneous Anaplastic T-Cell and Oro-Gastrointestinal Tract Mucosa-Associated B-Cell Lymphomas

Blood ◽  
1997 ◽  
Vol 90 (10) ◽  
pp. 4116-4125 ◽  
Author(s):  
Janet J. Bijl ◽  
Johan W. van Oostveen ◽  
Jan M.M. Walboomers ◽  
Anja Horstman ◽  
Adriaan J.C. van den Brule ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
B Cell ◽  
Expression Pattern ◽  
Gene Expression Pattern ◽  
Lymphoid Cells ◽  
B Cell Lymphomas ◽  
Preferential Expression ◽  
T Cell Lymphomas ◽  
Hodgkin's Lymphomas

Abstract Most of the 39 members of the homeobox (HOX) gene family are believed to control blood cell development. HOXC4 and HOXC6 gene expression levels increase with differentiation of lymphoid cells. In contrast, HOXC5 is not expressed in the lymphoid lineage, but was found in lymphoid cell lines, representing the neoplastic equivalents of various differentiation stages of T and B lymphocytes. In the present study, we investigated the HOXC4, HOXC5, and HOXC6 gene expression pattern in 89 non-Hodgkin's lymphomas (NHLs) of different histologic subtypes and originating from different sites. Using RNA in situ hybridization and semiquantitative reverse transcription-polymerase chain reaction, we found expression of HOXC4 in 83 of 88 and HOXC6 in 77 of 88 NHLs and leukemias investigated. In contrast, HOXC5 expression was found in only 26 of 87 NHLs and appeared to be preferentially expressed by two specific subsets of lymphomas, ie, primary cutaneous anaplastic T-cell lymphomas (9 of 9) and extranodal marginal zone B-cell lymphomas (maltomas; 7 of 9). These results indicate that, in contrast to HOXC4 and HOXC6, HOXC5 shows a type- and site-restricted expression pattern in both T- and B-cell NHLs.

scholarly journals Expression of the c-kit receptor in human lymphomas is restricted to Hodgkin's disease and CD30+ anaplastic large cell lymphomas

Blood ◽  
1994 ◽  
Vol 83 (3) ◽  
pp. 785-792 ◽  
Author(s):  
A Pinto ◽  
A Gloghini ◽  
V Gattei ◽  
D Aldinucci ◽  
V Zagonel ◽  
...  
Keyword(s):  
Lymph Node ◽  
Tumor Cells ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Large Cell ◽  
Lymphoid Cells ◽  
Receptor Protein ◽  
Cell Phenotype ◽  
Northern Blot Hybridization ◽  
Kit Receptor

Abstract The product of the proto-oncogene c-kit is a transmembrane receptor protein that plays an important role in the regulation of normal and neoplastic hematopoiesis via the interaction with its specific ligand termed stem cell factor. To examine whether c-kit product is possibly involved in the pathogenesis of human lymphomas, we analyzed the expression of the c-kit protein in neoplastic cells from a variety of lymphoid tumors by immunostaining of lymph node frozen sections with the 17F11 antibody, detecting an extracellular epitope of the c-kit receptor, and of c-kit RNA by Northern blot hybridization. Of 24 nonHodgkin's lymphomas (NHL) of B- and T-cell phenotype, none expressed immunodetectable c-kit protein that was also not evidenced in lymphoid cells of reactive lymph nodes and normal tonsils. In contrast, c-kit protein was expressed by Reed-Sternberg cells and their mononuclear variants from 11 of 21 Hodgkin's disease (HD) cases, and in tumor cells from 11 of 16 cases of CD30+ anaplastic large cell lymphoma (ALCL). c-kit specific mRNA was also detected in lymph node tissues from HD and ALCL cases but not in neoplastic tissues from NHL other than ALCL. In addition, c-kit/CD30+ tumor cells were evidenced by flow cytometry in a patient displaying massive bone marrow involvement by ALCL. With the exclusion of lymphocyte predominance cases of HD that resulted c-kit expression and the other histologic subtypes of HD or the immunologic phenotype of tumor cells (B, T, nonB-nonT) in both HD and ALCL. The highly restricted expression of the c-kit product among human lymphomas to HD and ALCL provides a further biologic link between these two closely related lymphoma entities.

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