Characterization of the T-cell receptor gamma chain gene rearrangements as an adjunct tool in the diagnosis of T-cell lymphomas in the gastrointestinal tract of cats

Gress, V.; Wolfesberger, Birgitt; Fuchs‐Baumgartinger, Andrea; Nedorost, Nora; Saalmüller, Armin; Schwendenwein, Ilse; Rütgen, Barbara C.; Hammer, Sabine E.

doi:10.1016/j.rvsc.2016.07.004

Cited by 20 publications

(18 citation statements)

References 12 publications

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“…Recently, a Japanese group developed multiplex PCR assays to increase the coverage of possible IGH or TCRG gene rearrangements in feline B‐ and T‐cell neoplasms and to reduce the number of PCR reactions . In a former experiment, we studied a cohort of 36 histologically confirmed feline intestinal T‐cell lymphoma cases, clonality was detected in 86% of the formalin‐fixed and paraffin‐embedded (FFPE)‐derived samples, proving that these primers can successfully be used even with archived material …”

Section: Introductionmentioning

confidence: 99%

Characterization of a PCR‐based lymphocyte clonality assay as a complementary tool for the diagnosis of feline lymphoma

Hammer

Groiss

Fuchs‐Baumgartinger

et al. 2016

Vet Comparative Oncology

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Differentiation between resident mature lymphocyte populations and small cell lymphoma cannot be made by cytological review alone and remains challenging in histopathological review. These cases warrant application of complementary tools like PCR-based immunoglobulin (IG) and T-cell receptor (TCR) clonality testing for confirmation. In this prospective study, diagnostic sensitivity and specificity of different primer sets for routine diagnosis of feline TCR gamma (TCRG) and complete IG heavy chain (IGH) gene rearrangements were assessed. Fine needle aspirates from 20 feline lymphoma cases and lymph node material from 10 cats without hematopoietic neoplasia were subjected to clonality testing. Feline lymphoma cell lines and previously confirmed patient material served as positive control. Detection limits for clonal populations within a polyclonal background was 90% for B-cells and 50% for T-cells. Diagnostic sensitivity and specificity of the clonality assay were 70% and 90%. Overall diagnostic accuracy was 77%, positive predictive value 93% and negative predictive value 60%.

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Section: Introductionmentioning

confidence: 99%

Characterization of a PCR‐based lymphocyte clonality assay as a complementary tool for the diagnosis of feline lymphoma

Hammer

Groiss

Fuchs‐Baumgartinger

et al. 2016

Vet Comparative Oncology

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“…The reported sensitivity for detecting a clonal TRG by PCR in T‐cell neoplasms has been relatively high, with 5/7 studies reporting sensitivities ≥79% . The sensitivity for detecting a clonal IGH receptor among feline B‐cell neoplasms has been historically lower, with sensitivity values ranging from 34% to 89% .…”

Section: Introductionmentioning

confidence: 99%

Assessment of immunoglobulin heavy chain, immunoglobulin light chain, and T‐cell receptor clonality testing in the diagnosis of feline lymphoid neoplasia

Rout

Burnett

Yoshimoto

et al. 2019

Veterinary Clinical Pathol

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Background: Differentiation between neoplastic and reactive lymphocytic proliferations can be challenging in cats. PCR for antigen receptor rearrangements (PARR) testing is a useful diagnostic tool to assess clonality of a lymphoid population.Previous feline PARR studies evaluated clonality of complete immunoglobulin heavy chain V-D-J (IGH-VDJ) and T-cell receptor gamma (TRG) gene rearrangements. Objectives:We aimed to evaluate the sensitivity and specificity of feline PARR primers targeting complete IGH-VDJ and TRG rearrangements, as well as incomplete IGH-DJ, kappa deleting element (Kde), and immunoglobulin lambda light chain (IGL) gene rearrangements in defined feline neoplasms and nonneoplastic controls. Methods: Fluorescently labeled PCR primers were designed to amplify complete IGH-VDJ, incomplete IGH-DJ, Kde, IGL, and TRG gene rearrangements in two multiplexed PCR reactions, and PCR products were analyzed by fragment analysis. Fresh tissue samples from 12 flow cytometrically confirmed B-cell lymphomas, 26 cytologically confirmed gastric and renal lymphomas of presumed B-cell origin, 30 flow cytometrically confirmed T-cell leukemias, and 11 negative control cats were tested. Results: Using four immunoglobulin primer sets (IGH-VDJ, IGH-DJ, Kde, and IGL), clonal immunoglobulin rearrangements were detected in 87% (33/38) of the presumed B-cell neoplasms. The IGH-VDJ reaction alone only detected clonality in 50% (19/38) of these cases. TRG rearrangements were clonal in 97% (29/30) of the T-cell leukemia cases. All negative control samples had polyclonal immunoglobulin and TRG rearrangements. Conclusions: The PARR assay developed in this study is useful for assessing clonality in feline lymphoid neoplasms. Clonality assessment of incomplete IGH-DJ, Kde, and IGL rearrangements helped identify clonal B-cell neoplasms not detected with complete IGH-VDJ PARR alone. K E Y W O R D S antigen receptor rearrangement, lymphoma, T-cell receptor gamma S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Rout ED, Burnett RC, Yoshimoto JA, Avery PR, Avery AC. Assessment of immunoglobulin heavy chain, immunoglobulin light chain, and T-cell receptor clonality testing in the diagnosis of feline lymphoid neoplasia. Vet Clin Pathol. 2019;48(Suppl. 1):45-58. https ://doi.

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“…Small cell GI LSA closely resembles feline inflammatory bowel disease (IBD) in its clinical presentation,2 with both diseases having poorly defined etiologies. Various risk factors including genetic and molecular alterations,3, 4, 5 diet,3, 6, 7 and chronic inflammation8, 9, 10 have been linked to the development of both disorders. Still other studies have suggested an association between chronic mucosal inflammation and the progression of IBD to pronounced dysplasia in the GI tract 11, 12, 13, 14…”

Section: Introductionmentioning

confidence: 99%

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

Garraway

Johannes

Bryan

et al. 2018

Veterinary Internal Medicne

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BackgroundThe gastrointestinal (GI) microbiota in healthy cats is altered in IBD. Little research has been performed to identify whether specific bacterial groups are associated with small cell GI lymphoma (LSA).HypothesisMucosal bacteria, including Enterobacteriaceae and Fusobacterium spp., are abundant in intestinal biopsies of cats with small cell GI LSA compared to cats with IBD.AnimalsFourteen cats with IBD and 14 cats with small cell GI LSA.MethodsRetrospective case control study. A search of the medical records was performed to identify cats diagnosed with IBD and with GI LSA. Bacterial groups identified by FISH in GI biopsies were compared between cohorts and correlated to CD11b+ and NF‐κB expression.Results Fusobacterium spp. (median; IQR bacteria/region) were higher in cats with small cell GI LSA in ileal (527; 455.5 – 661.5; P = .046) and colonic (404.5; 328.8 – 455.5; P = .016) adherent mucus, and combined colonic compartments (free mucus, adherent mucus, attaching to epithelium) (8; 0 – 336; P = .017) compared to cats with IBD (ileum: 67; 31.5 – 259; colon: 142.5; 82.3 – 434.5; combined: 3; 0 – 34). Bacteroides spp. were higher in ileal adherent mucus (P = .036) and 3 combined ileal compartments (P = .034) of cats with small cell GI LSA. There were significant correlations between Fusobacterium spp. totals and CD11b+ cell (P = .009; rs .476) and NF‐κB expression (P = .004; rs .523).ConclusionsThe bacterial alterations appreciated might be influential in development of small cell GI LSA, and should drive further studies to elucidate the effects of microbial‐mediated inflammation on GI cancer progression.

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Characterization of the T-cell receptor gamma chain gene rearrangements as an adjunct tool in the diagnosis of T-cell lymphomas in the gastrointestinal tract of cats

Cited by 20 publications

References 12 publications

Characterization of a PCR‐based lymphocyte clonality assay as a complementary tool for the diagnosis of feline lymphoma

Characterization of a PCR‐based lymphocyte clonality assay as a complementary tool for the diagnosis of feline lymphoma

Assessment of immunoglobulin heavy chain, immunoglobulin light chain, and T‐cell receptor clonality testing in the diagnosis of feline lymphoid neoplasia

Relationship of the mucosal microbiota to gastrointestinal inflammation and small cell intestinal lymphoma in cats

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