Scripties UMCG - Rijksuniversiteit Groningen
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Clinical application of Thymus and Activated Regulated Chemokine (TARC) in classical Hodgkin lymphoma

(2017) Veldman, C. (Carlijn)

Thymus and activated regulated chemokine (TARC) is recently introduced as a tissue and blood biomarker for classical Hodgkin’s Lymphoma (cHL). TARC-immunohistochemistry is currently performed in diagnostics and circulating TARC-levels are used for evaluation of treatment response. The aim of the current study was to analyze the additive value of TARC-immunohistochemistry and to investigate confounders of circulating TARC and TARC-levels in diseases which might mimic cHL.
Design and Methods
All tissue samples stained for TARC were identified using PALGA to investigate the additive value of TARC-immunohistochemistry. A total of 107 cases were included in this analysis, including 56 cases with cHL. Three different study cohorts were used to analyze other factors or disease states that might influence circulating TARC-levels. The first cohort consisted of tissue samples from 8 sarcoidosis patients and 10 thymoma patients, diseases which might mimic the clinical presentation of cHL. The second and third cohort were used to analyze confounding factors on circulating TARC-levels. The second cohort consisted of serum TARC-levels from 121 cHL patients during treatment and follow-up, to analyze normal fluctuations of TARC after successful treatment. Pre-treatment samples of the same cohort were used to analyze other confounding factors. The third cohort consisted of 83 plasma samples from patients with sepsis. Tissue samples were incubated with a goat-anti-human TARC antibody after heat induced antigen retrieval. Circulating TARC-levels were measured using enzyme-linked immunosorbent assay. A multivariate analysis was performed to investigate confounders.
Fifty-four of 56 cHL cases showed TARC-expression in the tumor cells. TARC-staining was supportive in 6 of 9 cases with a weak CD30-expression and for further determination of doubtful cells in other lymphoma subtypes. Four of 8 sarcoidosis patients showed TARC-expression in the tissue. None of the thymoma patients showed elevated TARC-expression compared to the normal thymus. Circulating TARC-levels of patients in persistent remission remained stable below 1.000 pg/mL. Relapse patients showed rising circulating TARC-levels before relapse was diagnosed. Circulating TARC-levels correlate with metabolic tumor volume. No significant higher circulating TARC-levels were seen in patients with various infectious states compared to healthy volunteers.
Immunohistochemical TARC-staining was supportive for further determination of doubtful cells in other types of lymphomas or in cases of weak CD30 expression. Elevated circulating TARC-levels could be expected in patients with sarcoidosis, in contrast to thymoma patients or patients with an active infection. Circulating TARC-levels of patients in persistent remission remain stable during follow-up and relapse patients showed rising TARC-levels before relapse was diagnosed. Circulating TARC-levels are mainly influenced by metabolic tumor volume.

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