Elevated serum thymidine kinase activity in canine splenic hemangiosarcoma^*

Abstract

Thymidine kinase 1 (TK1) is a soluble biomarker associated with DNA synthesis. This prospective study evaluated serum TK1 activity in dogs presenting with hemoabdomen and a splenic mass. An ELISA using azidothymidine as a substrate was used to evaluate TK1 activity. Sixty-two dogs with hemoabdomen and 15 normal controls were studied. Serum TK1 activity was significantly higher in dogs with hemangiosarcoma (HSA) than in normal dogs (mean ± SEM = 17.0 ± 5.0 and 2.01 ± 0.6, respectively), but not dogs with benign disease (mean ± SEM = 10.0 ± 3.3). Using a cut-off of 6.55 U/L, TK activity demonstrated a sensitivity of 0.52, specificity of 0.93, positive predictive value of 0.94 and negative predictive value of 0.48 for distinguishing HSA versus normal. When interval thresholds of <1.55 and >7.95 U/L were used together, diagnostic utility was increased. Serum TK1 evaluation may help to discriminate between benign disease and HSA in dogs with hemoabdomen and a splenic mass.

A comparison of microRNA expression profiles from splenic hemangiosarcoma, splenic nodular hyperplasia, and normal spleens of dogs

“…Another group found a contradictory function, in that mir-424 regulated VEGF and bFGF signaling by reducing expression of receptors for those cytokines and increased expression of mir-424 led to reduced proliferation and migration of endothelial cells [60]. This group also found that VEGF and bFGF had stimulatory effects on mir-424 expression, indicating that increased levels of VEGF, as seen in hemangiosarcoma, may have led to the finding of mir-424 being overexpressed, participating in a negative feedback loop [14, 60]. While it remains clear that mir-424 plays a role in angiogenesis, further studies are warranted to evaluate its specific role in canine hemangiosarcoma.…”

“…Many studies have attempted to identify repeatable measures or other techniques that might distinguish malignant from benign masses [5, 9–14]. For instance, mass-to-splenic volume ratio and splenic weight as a percentage of body weight have been used to differentiate malignant from benign splenic lesions, with hemangiosarcoma masses being smaller in both categories [5].…”

“…Also, some clinicians recommend not aspirating the spleen in suspected cases of hemangiosarcoma due to risk of tumor rupture and seeding of the tumor into the abdomen [5, 6]. Testing of blood with multi-parameter flow cytometry and measuring levels of vascular endothelial growth factor and thymidine kinase have been evaluated, but have not been found to be definitive diagnostic tools [12–14]. It is clear that additional work needs to be done to develop a minimally invasive pre-surgical diagnostic test to differentiate hemangiosarcoma from other splenic masses.…”

Cancer Screening Tests for Small Animals

“…2,4,5 In veterinary species, high levels of serum TK1 compared with normal range are detected in canine lymphoma, splenic hemangiosarcoma, and feline lymphoma. [2][3][4][5][6][7][8] Solid tumors in dogs and humans do not show consistently increased levels precluding serum TK1 levels as a general biomarker for all cancer histologies. 3 However, it is used in humans for breast, lung, and colorectal cancer.…”

Serum thymidine kinase activity in clinically healthy and diseased cats: a potential biomarker for lymphoma

“…Elevated sTK activity has also been reported in dogs with splenic haemangiosarcoma and suggested to be due to the high proliferation rate and intimate association with the vasculature of this tumour. 17 Limitations of the current study include the variable storage conditions of samples. However, it has been shown that sTK stability is maintained despite different durations and temperatures of storage, so this was not thought to have influenced the results.…”