Flow Cytometric Characterization and Clinical Outcome of <scp>CD</scp>4+ T‐Cell Lymphoma in Dogs: 67 Cases

Avery, P.; Burton, Jenna H.; Bromberek, Julia L.; Seelig, Davis; Elmslie, Robyn; Correa, Stephanie Shank; Ehrhart, E. J.; Morley, Paul S.; Avery, Anne C.

doi:10.1111/jvim.12304

Cited by 62 publications

(107 citation statements)

References 27 publications

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“…Histopathology is considered the gold standard for characterization of lymphoma in dogs, but is more commonly reserved for cases where cytology is inconclusive. Recent studies have demonstrated that FC of LN aspirates can provide correlates with histopathology, such as determination of immunophenotype and expression of antigens associated with prognosis in subtypes of canine BCL and TCL . For example, low levels of MHC II expression were predictive of poor outcome in dogs with BCL .…”

Section: Discussionmentioning

confidence: 99%

Expression of Apoptosis‐regulating Proteins Bcl‐2 and Bax in Lymph Node Aspirates from Dogs with Lymphoma

Meichner

Fogle

English

et al. 2016

Veterinary Internal Medicne

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BackgroundDysregulated apoptosis is a hallmark of tumorigenesis, and is also involved in resistance to cytotoxic treatment, and might be relevant in lymphoma in dogs.Hypothesis/ObjectivesThat Bcl‐2/Bax expression patterns differ between lymphoma immunophenotypes, and that Bcl‐2/Bax ratio is correlated with prognosis.AnimalsFifty‐five client‐owned dogs with multicentric lymphoma and 5 healthy dogs.MethodsProspective, case–control study. We compared 3 methods (flow cytometry, qRT‐PCR, Western blot) for Bcl‐2 and Bax quantification in a subset of dogs. The effect of time on Bcl‐2/Bax ratios measured by flow cytometry was assessed in lymphoma cell lines. Immunophenotype and Bcl‐2/Bax expression by flow cytometry were determined in LN aspirates from all dogs with multicentric lymphoma compared to healthy dogs. Progression‐free survival (PFS) was retrospectively evaluated in a group of dogs all receiving similar treatment.ResultsBcl‐2/Bax ratios remain consistent for at least 5 days after sample collection. Bcl‐2/Bax ratio was higher in dogs with T‐cell lymphoma (TCL; median 0.97, range 0.37–1.36) compared to B‐cell lymphoma (BCL; median 0.36, range 0.07–1.45) (P < .0001) and normal dogs (median 0.36, range 0.21–0.48) (P = .0006), respectively. Dogs with Bcl‐2/Bax ratios higher than the median of the group experienced a median PFS of 101 days and dogs with ratios equal and lower than the median had PFS of 130 days (P = .19).Conclusions and clinical importanceHigher intrinsic resistance to apoptosis following cytotoxic treatment might contribute to the less favorable prognosis associated with multicentric TCL in dogs. Whether Bcl‐2/Bax will be helpful to identify canine BCL and TCL with more aggressive and more indolent behavior, respectively, should be evaluated in larger prospective clinical studies.

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Section: Discussionmentioning

confidence: 99%

Expression of Apoptosis‐regulating Proteins Bcl‐2 and Bax in Lymph Node Aspirates from Dogs with Lymphoma

Meichner

Fogle

English

et al. 2016

Veterinary Internal Medicne

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“…However, neoplastic cells in both human and canine PTCL, NOS are typically positive for mature T-cell markers, including CD3 and CD5 [39,40]. Phenotypic aberrancy in hPTCL, NOS, as evident by loss of either CD5 and CD7 or CD4/CD8 dual positivity or negativity are also common [59–61].…”

Section: T-cell Neoplasmsmentioning

confidence: 99%

The Comparative Diagnostic Features of Canine and Human Lymphoma

Seelig

Avery

Ehrhart

et al. 2016

Veterinary Sciences

102

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The non-Hodgkin lymphomas (NHLs) are a heterogeneous family of lymphoid malignancies that are among the most common neoplasms of both dogs and humans. Owing to shared molecular, signaling, incidence, and pathologic features, there is a strong framework supporting the utilization of canine lymphoma as a comparative, large animal model of human NHL. In alignment with the biologic similarities, the current approach towards the diagnosis and classification of canine lymphoma is based upon the human World Health Organization guidelines. While this approach has contributed to an increasing appreciation of the potential biological scope of canine lymphoma, it has also become apparent that the most appropriate diagnostic philosophy must be multimodal, namely by requiring knowledge of microscopic, immunophenotypic, and clinical features before establishing a final disease diagnosis. This review seeks to illustrate the comparative similarities and differences in the diagnosis of canine lymphoma through the presentation of the microscopic and immunophenotypic features of its most common forms.

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“…The utility of flow cytometry is particularly evidenced by T‐zone lymphoma (TZL) which is routinely diagnosed by flow cytometry based on an expansion of small to intermediate sized CD3 + CD5 + T‐cells with characteristic loss of the pan‐leukocyte marker CD45 . T‐zone lymphoma is an indolent T‐cell lymphoma that is clinically important to distinguish from more aggressive types of peripheral T‐cell lymphomas . Furthermore, diagnosis of T‐zone lymphoma by flow cytometry has been shown to reliably predict a distinct histologic pattern and cytomorphology consistent with the disease entity …”

Section: Introductionmentioning

confidence: 99%

Canine CD4+ T‐cell lymphoma identified by flow cytometry exhibits a consistent histomorphology and gene expression profile

Harris

Hughes

Ehrhart

et al. 2019

Vet Comparative Oncology

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T‐cell lymphomas (TCL) are a diverse group of neoplasms with variable diagnostic features, pathophysiologies, therapeutic responses and clinical outcomes. In dogs, TCL includes indolent and aggressive tumours such as T‐zone lymphoma (TZL) and peripheral T‐cell lymphoma (PTCL), respectively. Delineation of molecular subtypes and investigation into underlying pathophysiologies of aggressive TCLs remains inadequate. We investigate the correlations between flow cytometry and histopathology of 73 cases of nodal TCL. The majority of cases (82.2%) were characterized as CD4+ TCL by flow cytometry. Fewer cases were classified as CD8+ TCL (6.8%) or CD4−CD8− TCL (11.0%). All cases, regardless of immunophenotype, exhibited conserved histologic features consistent with the WHO classification of PTCL. Histologic subsets of PTCL corresponding to immunophenotypic features were not identified. Neoplastic cell size determined by flow cytometry correlated significantly with mitotic rate. RNA‐seq was performed on a subset of CD4+ PTCL cases (n = 6) and compared with sorted control CD4+ T‐cells. The gene expression pattern of CD4+ PTCL was similar between all cases regardless of breed. PTCL was enriched in pathways representing G‐coupled protein receptor signalling, extracellular matrix remodelling and vascular development, immune signalling and mitotic activity. Furthermore, global gene expression changes were consistent with downregulation of PTEN signalling and upregulation of the MTOR‐PI3K‐ATK axis. In this study, we evaluated the correlations between flow cytometry, histopathology and gene expression within a large cohort of nodal TCLs. We further demonstrate the ability of flow cytometry to identify a subtype of T‐cell lymphoma, CD4+ PTCL, with a uniform histomorphology and gene expression profile.

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Flow Cytometric Characterization and Clinical Outcome of CD4+ T‐Cell Lymphoma in Dogs: 67 Cases

Cited by 62 publications

References 27 publications

Expression of Apoptosis‐regulating Proteins Bcl‐2 and Bax in Lymph Node Aspirates from Dogs with Lymphoma

Expression of Apoptosis‐regulating Proteins Bcl‐2 and Bax in Lymph Node Aspirates from Dogs with Lymphoma

The Comparative Diagnostic Features of Canine and Human Lymphoma

Canine CD4+ T‐cell lymphoma identified by flow cytometry exhibits a consistent histomorphology and gene expression profile

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