A clinical evaluation of the TK 210 ELISA in sera from breast cancer patients demonstrates high sensitivity and specificity in all stages of disease

Abstract

Thymidine kinase (TK1) is an enzyme involved in DNA synthesis that leaks into the blood as a result of high cell turnover, particularly in the case of cancer. Serum TK1 activity has been used for prognosis and monitoring of leukemia and lymphoma patients for many years. Here, we describe the first clinical results with the newly developed TK 210 ELISA from AroCell AB. Sera from 124 breast cancer patients with known TNM classification along with sera from 53 healthy females were analyzed by TK 210 ELISA for TK1 protein and TK1 activity levels by the 3[H]-deoxythymidine (dThd) phosphorylation assay. The limit of detection for the TK 210 ELISA was 0.17 ng/ml, and 60 % of the sera from female blood donors were below this value. The median TK1 levels found in sera from breast cancer patients with T1 to T4 stage disease were 0.31, 0.46, 0.47, and 0.55 ng/ml, and these levels significantly differed from healthy controls. The median values of the biomarker CA 15-3 were also increased in patient sera from T1 to T4 patients (16, 34, 36, 40 U/ml, respectively). TK 210 ELISA showed significantly higher sensitivity for the T1 and T2 breast cancer patients compared to the TK activity assay. The combination of the TK1 ELISA and CA 15-3 biomarkers demonstrated a significant increase in sensitivity up to 15 % compared to each marker alone. This evaluation of the TK 210 ELISA strongly suggests that it can provide independent and complementary information for patients with breast cancer.Electronic supplementary materialThe online version of this article (doi:10.1007/s13277-016-5024-z) contains supplementary material, which is available to authorized users.

The combination of AroCell TK 210 ELISA with Prostate Health Index or prostate‐specific antigen density can improve the ability to differentiate prostate cancer from noncancerous conditions

“…This assay is suitable for determinations of TK1 protein levels in sera from patients with solid and haematological malignancies (http://www.arocell.com). Several studies have been performed demonstrating the clinical value of STK1 activity and protein‐based assays in different cancer diseases, but only a limited number are concerned with PCa . Some studies describing other TK ELISA methods have been published in recent years, and there are some other TK ELISA tests currently commercially available, but with no reported results with PCa.…”

“…The TK1 protein levels in serum samples were determined using the AroCell TK 210 ELISA according to the manufacturer’s instructions (http://www.e-labeling.eu/ARO1001-15-4). In the TK 210 ELISA, we have used horseradish peroxidase‐labelled streptavidin to detect the biotin‐labelled antibody‐enzyme complex and 3,3′,5,5′‐tetramethylbenzidine as the substrate solution.…”

“…This may be due to the fact that some serum TK1 forms found in subjects with solid tumours have a low enzyme activity but are still detectable with an ELISA using two monoclonal antibodies against specific TK1 antigenic sites (http://www.arocell.com). The study demonstrated that the AroCell TK 210 ELISA showed significantly greater sensitivity for breast cancer patients compared to a TK1 activity assay. Furthermore, this study also demonstrated that a combination of TK1 protein determinations and the breast cancer biomarker CA 15‐3 was more accurate in differentiating T2 breast cancer patients from healthy controls than either of them alone …”

“… The study demonstrated that the AroCell TK 210 ELISA showed significantly greater sensitivity for breast cancer patients compared to a TK1 activity assay. Furthermore, this study also demonstrated that a combination of TK1 protein determinations and the breast cancer biomarker CA 15‐3 was more accurate in differentiating T2 breast cancer patients from healthy controls than either of them alone …”

A meta‑analysis of serological thymidine kinase 1 as a marker for colorectal benign and malignant tumor risk assessment

“…TK1 is a kinase enzyme that converts deoxythymidine to deoxythymidine monophosphate and is involved in the synthesis of DNA, and thus related to cell growth rate (proliferation). The new-generation STK1p concentration assay shows an area under the curve (AUC) value of 0.96 (18), and is a more reliable assay than the serum TK activity (19,20) and serum TK1 sandwich ELISA (21) assays. Low STK1p values are associated with a better prognosis (16,18,(22)(23)(24)(25)(26)(27).…”