Clinical performance of a commercially available thymidine kinase 1 assay for diagnosis of lymphoma in 42 hospitalized horses (2017‐2020)

Abstract

Background Antemortem definitive diagnosis of lymphoma in horses is often difficult. Thymidine kinase 1 (TK1) assay is a potentially useful biomarker for lymphoma in horses. Hypothesis/objectives To report the clinical performance of a commercially available TK1 assay for diagnosis of lymphoma in horses. We hypothesized that there would be no association between serum TK1 activity and a diagnosis of lymphoma in horses. Animals Forty‐two hospitalized horses, 14 with a definitive diagnosis of lymphoma, 4 with other neoplasia, and 24 with inflammatory disease. Methods Retrospective medical record review, groups were compared via Kruskal‐Wallis and Mann‐Whitney tests, and logistic regression was performed. Results Median (range) TK1 was 3 U/L (0.4‐17.7 U/L) in horses with lymphoma and 3.9 U/L (0.8‐94 U/L) in horses without lymphoma (P = .59). There was no significant difference in total protein between horses with and without lymphoma (6.6 g/dL [5.5‐8.3 g/dL] vs 6.6 g/dL [4.7‐10.4 g/dL]; P = .83). There was no significant difference in fibrinogen between horses with and without lymphoma (447 [100‐1364] mg/dL vs 433 [291‐2004] mg/dL; P = .47). On logistic regression, serum TK1 activity was not associated with a diagnosis of lymphoma (odds ratio, 0.97; 95% confidence interval, 0.9‐1.05, P = .48). Conclusion and Clinical Importance Serum TK1 values were not predictive of lymphoma diagnosis in this cohort of horses.

Markers for internal neoplasia in the horse

“…There is a high production of this enzyme in fast‐proliferating neoplastic cells, and increased serum activity is caused by the leakage of TK1 after their death (Hallek et al., 1992 ); thus, the TK1 activity in serum correlates with the proliferative activity of the tumour (Hallek et al., 1992 ). However, the enzyme is highly unspecific as it can be released from many cells, including hepatocytes, hematopoietic and various neoplastic cells (Moore et al., 2021 ; Tanaka et al., 1993 ).…”

“…Inflammatory diseases cause a temporary elevation in TK1 activity in humans and dogs, most probably due to the proliferation of the leucocytes and their lysis at the site of inflammation (Gronowitz et al., 1983 ; Nakamura et al., 1997 ). A modest increase in the serum activity of TK1 was detected in a few horses with various inflammatory conditions (Larsdotter et al., 2015 ; Moeller et al., 2020 ; Moore et al., 2021 ).…”

“…A few reports of utilising TK1 as a biomarker of hematopoietic tumours in horses (lymphoma and multiple myeloma) were quite promising (Larsdotter et al, 2015;Moeller et al, 2020;Wang et al, 2021), but other studies showed that its performance is below expectations because false-negative (Luethy et al, 2019;Moore et al, 2021) and false-positive results are reported (Moeller et al, 2020). Moore et al (2021) described no significant difference between the TK1 activity in equids with inflammatory disorders, hematopoietic and other neoplasia. On the other hand, Wang et al (2021) found that TK1 performed well in distinguishing between horses with suspected/confirmed lymphoma and tumour-free controls.…”

“…On the other hand, Wang et al (2021) found that TK1 performed well in distinguishing between horses with suspected/confirmed lymphoma and tumour-free controls. Those discrepancies might be partially due to different assays used in both studies, with the method determining the TK1 activity using [ 3 H]-dThd as the substrate being more promising (Moore et al, 2021;Wang et al, 2021).…”

Primary hyperparathyroidism in horses: What can we learn from human medicine?

“…Elevated levels of PTH-related peptide (PTH-rP) were reported in one horse affected with multiple myeloma (Barton et al, 2004). Although elevated serum thymidine kinase-1 (TK1) levels have been proposed as useful diagnostic indicators of lymphoma in horses (Larsdotter et al, 2015), later studies yielded conflicting results (Moore et al, 2021;Wang et al, 2021). Although the authors concluded that a paraneoplastic explanation for hypercalcemia could be ruled out based on a normal TK1 level in their patient, caution in that regard is recommended until better cancer biomarkers with improved positive and negative predictive values have been evaluated and validated for both equine and human medicine.…”