T‐Cell receptor variable (V) gene usage by lymphoid populations in T‐cell lymphoma

Smith, Joan K.; Lane, A. C.; Hodges, Elizabeth; Reynolds, Wendy M.; Howell, W. M.; Jones, David B.; Janson, Carl Harald

doi:10.1002/path.1711660205

Cited by 13 publications

(2 citation statements)

References 17 publications

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“…These data suggest an association in AILD that has not been observed in previous studies of T cell leukemias and lymphomas. 36 These data also explain the discrepancy between TCR␤ protocols in this study, as McCarthy's primers lack homology with BV families V2, V4, and V8. 24 In three cases functional TCR␤ gene rearrangements were detected in the absence of TCR␥ gene rearrangements, contrary to expectation where nonfunctional TCR␥ genes are usually associated with functional TCR␤ gene rearrangements.…”

Section: Discussionmentioning

confidence: 71%

Frequent T and B Cell Oligoclones in Histologically and Immunophenotypically Characterized Angioimmunoblastic Lymphadenopathy

Smith¹,

Hodges²,

Quin³

et al. 2000

The American Journal of Pathology

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The identification of clonal rearrangements of T cell receptor (TCR) genes is central to the diagnosis of T cell lymphomas. However, in angioimmunoblastic lymphadenopathy (AILD), first described as a nonneoplastic proliferation associated with immunodeficiency, the heterogeneity of TCR and IgH gene rearrangements suggest that some cases may harbor multiple lymphoid clones. In this study we have isolated DNA from archival paraffin biopsy material from 22 cases of AILD identified on the basis of classical histological and immunohistochemical features with the aim of establishing the occurrence of clones and oligoclones, the frequency of TCR and immunoglobulin heavy chain (IgH) variable (v) gene use, and the relationship of these findings to the presence of Epstein-Barr virus. DNA extracted from the biopsies was amplified using the polymerase chain reaction (PCR) and sequenced to detect functional and nonfunctional gene rearrangements. Epstein-Barr virusencoded short RNA species (EBERs) were detected using in situ hybridization combined with immunochemistry to identify the phenotype of the EpsteinBarr virus-infected cells. Fifty-seven clonal products were found in 20/22 patients: TCR␥ clonal products were identified in 16/22, TCR␤ clonal products in 16/22 and IgH clonal products in 6/22 cases. Oligoclonal PCR products were seen for TCR in 3/22 and for IgH in 3/22 cases. In one biopsy PCR products from all reactions were polyclonal. Sequence analysis revealed functional TCR␥, TCR␤, and IgH sequences in 6/12, 9/11, and 8/8 cases, respectively. Functional TCR and/or IgH oligoclones were detected in 6/20 (30%) cases. In addition, nonfunctional TCR and IgH sequences were found in 11 cases. EBERs were identified in 18/20 cases varying from occasional to 25 to 30% nuclei staining and were associated with both T and B cells, although the majority were of indetermi- Early reports of AILD stressed the nonneoplastic nature of this disease, 1,2 noting that neither the cytology nor the pattern of infiltration seen in biopsies or autopsies was that of a neoplasm. The disease was thought to be due to abnormal immune regulation, the majority of patients dying of infections, often with opportunistic organisms.2 An association with lymphoma was, however, noted by Lukes and Tindle, 3 who reported the development of immunoblastic lymphoma in 3 of their 32 patients. Subsequently, there has been controversy over the separation of AILD from AILD with immunoblastic lymphoma (IBL) based on histological features such as atypical clear cells, which has contributed to the variation in the reported incidence of lymphoma in AILD from 0 to 35%. 4 -6 In addition, both groups show clonality or lack of clonality. 4,7 Frizzera et al 8 has proposed that three AILDrelated disorders can be recognized as AILD, AILD-like dysplasia, and AILD-like peripheral T cell lymphoma (PTCL) based on a combination of morphology, phenotype, clonal-

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Section: Discussionmentioning

confidence: 71%

Frequent T and B Cell Oligoclones in Histologically and Immunophenotypically Characterized Angioimmunoblastic Lymphadenopathy

Smith¹,

Hodges²,

Quin³

et al. 2000

The American Journal of Pathology

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“…The few studies addressing the TCRV␤ repertoire analysis in PTCL found either no evidence for an overrepresentation of certain subfamilies 14,51,52 or a bias in the TCRV␤ subfamily frequency of the tumors different from ours. [53][54][55][56][57][58] Taking all of these data together, it is unlikely that there is a general TCRV␤ subfamily/ segment preference in PTCL, and it seems that TCRV␤ subfamily usage in a large series merely follows the random distribution of TCRV␤ subfamilies in normal individuals. 12,59 -63 The preference of the TCRJ␤2 cluster (14 tumors) to the TCRJ␤1 cluster (9 tumors) in our study fits in with the predominance of TCRJ␤2 rearrangements in precursor T-cell malignancies 64 and reflects differences in TCRJ␤ usage in reactive T-cell populations.…”

Section: Discussionmentioning

confidence: 99%

Identification of the Tumor Cells in Peripheral T-Cell Lymphomas by Combined Polymerase Chain Reaction-Based T-Cell Receptor β Spectrotyping and Immunohistological Detection with T-Cell Receptor β Chain Variable Region Segment-Specific Antibodies

Geissinger

Bonzheim

Krenács

et al. 2005

The Journal of Molecular Diagnostics

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Most nodal peripheral T-cell lymphomas (PTCL) originate from alphabeta-T cells, and they often contain reactive T cells that may hamper immunophenotyping. To specifically identify the neoplastic population in immunohistochemically stained slides, we assessed the heterogeneity of the T-cell receptor beta chain variable region (TCRVbeta). This region contains 65 gene segments, of which only one is expressed after rearrangement. To investigate PTCL, we developed a polymerase chain reaction assay to define the clonally rearranged TCRVbeta segment. Detecting the corresponding epitope with segment-specific antibodies enabled identification of tumor cells among the T cells. The TCRVbeta segment of the tumor cells was defined in 13 of 13 PTCL not otherwise specified and 11 of 13 angioimmunoblastic T-cell lymphomas. Antibodies corresponding to the respective TCRVbeta segment of the tumor were available for seven cases from each group. After applying these antibodies in combination with antibodies against CD3, CD5, CD4, CD8, and cytotoxic molecules, double stains were evaluated by confocal laser scanning microscopy. In 9 of 14 cases, less than 50% of T cells expressed the clonally rearranged TCRVbeta segment. Phenotypes defined in double stains differed from those obtained by conventional immunohistochemistry in 11 of 14 cases. The combination of TCRVbeta polymerase chain reaction and immunohistochemistry may facilitate more reliable detection and characterization of tumor cells in PTCL.

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Detection of T‐cell receptor β chain mRNA in frozen and paraffin‐embedded biopsy tissue using digoxigenin‐labelled oligonucleotide probes in situ

Hodges

Howell

Tyacke

et al. 1994

The Journal of Pathology

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In situ hybridization techniques using a cocktail of digoxigenin-labelled T-cell receptor (TcR) constant (C) region beta oligonucleotide probes were used to detect TcR beta mRNA in frozen and paraffin-embedded tissue sections. The specificity of the C beta cocktail was confirmed by Northern blot analysis. The TcR C beta cocktail successfully hybridized to T cells in frozen and paraffin-embedded tissue obtained from patients with inflammatory arthropathies, B- and T-cell non-Hodgkin's lymphoma (NHL), and reactive tonsillitis, and showed staining patterns comparable to those obtained by conventional immunohistological detection of T cells. This is the first report of in situ studies using labelled TcR C beta oligonucleotide probes and may indicate the feasibility of investigating clonal T-cell populations using digoxigenin-labelled clonospecific probes in clinical samples in situ.

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T‐Cell receptor variable (V) gene usage by lymphoid populations in T‐cell lymphoma

Cited by 13 publications

References 17 publications

Frequent T and B Cell Oligoclones in Histologically and Immunophenotypically Characterized Angioimmunoblastic Lymphadenopathy

Frequent T and B Cell Oligoclones in Histologically and Immunophenotypically Characterized Angioimmunoblastic Lymphadenopathy

Identification of the Tumor Cells in Peripheral T-Cell Lymphomas by Combined Polymerase Chain Reaction-Based T-Cell Receptor β Spectrotyping and Immunohistological Detection with T-Cell Receptor β Chain Variable Region Segment-Specific Antibodies

Detection of T‐cell receptor β chain mRNA in frozen and paraffin‐embedded biopsy tissue using digoxigenin‐labelled oligonucleotide probes in situ

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