Abstract

Abstract Background: Thymidine Kinase 1 (TK1) is an ATP dependent enzyme involved in DNA precursor synthesis. It is released into the blood from cells undergoing un-controlled proliferation where it forms stable aggregates. Serum TK1 activity has been used as a biomarker for diagnosis and monitoring of hematological malignancies. Several commercial assays are available for measuring serum TK1 activity but they require radioactive materials or special instruments. To overcome these, AroCell has developed the TK 210 ELISA for TK1 protein measurements. In this study, we compared the performance of the TK 210 ELISA to that of the TK-Liaison assay on sera from subjects with hematological and solid tumors Experimental Procedures Sera from patients with hematologic malignancies (N=51) were collected at the University Hospital, Uppsala. Samples from solid tumors [breast cancer (n=60); subjects with benign prostate hyperplasia or prostate carcinoma (n=60)] along with blood donors (N=102) were collected at the University Medical Centre, Ljubljana. TK1 protein levels were determined with AroCell TK 210 ELISA and TK1 activity levels by the TK-Liaison assay. Results In blood donors, the TK1 protein levels were in the range of 0.1 to 0.35 µg/L with a median value of 0.2. Men had a higher median value TK1 protein levels compared to women (0.21 vs 0.19) with no significant difference. Both the TK 210 ELISA and the TK-Liaison assays showed significantly higher TK1 levels in hematological and solid tumors compared to blood donors (P<0.0001). ROC curve analysis demonstrated that across all malignancies, at 96% specificity, TK 210 ELISA (cut-off value of 0.34 µg/L) gave a higher sensitivity of 0.43 compared to TK-Liaison assay (cut-off value of 10 U/L) of 0.36. The performance of the assays differed depending on the type of malignancy, TK 210 ELISA and TK-Liaison had a similar sensitivity (0.65) for hematological malignancies. However, in the case of solid tumors, TK 210 ELISA showed a higher sensitivity (0.35) compared to TK-Liaison (0.26) at a specificity of 0.96. A regression analysis of the TK 210 ELISA (y) and TK-Liaison (x) assays across all three groups gave an equation of y = 0.15 + 0.017x (rs = 0.80, n = 273). The correlation value in hematological malignancies was higher than in blood donors and solid tumors (0.95 vs. 0.67 and 0.50 respectively). Conclusions This study showed that the AroCell TK 210 ELISA has a similar sensitivity and specificity to the TKLiaison assay for hematological malignancies. However, the AroCell TK 210 ELISA demonstrated a higher sensitivity for TK1 in sera from subjects with solid tumors and this may facilitate the application of TK1 as a biomarker for solid tumors. Furthermore, the robustness and convenience of the ELISA not only overcomes the limitations of TK-Liaison but also widens the clinical applications of TK1 in cancer management. Citation Format: Jagarlamudi Kiran Kumar, Staffan Eriksson, Kerstin Hamberg Levedahl, Martin Höglund, Mojca Zupan, Joško Osredkar, Diana Cviič, Urska Furar. The assay of thymidine kinase 1 in sera from subjects with hematological and solid tumors with AroCell TK 210 ELISA: Comparison with TK-liaison assay and its clinical implications [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2232.

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