Comparison of diagnostic and prognostic performance of two assays measuring thymidine kinase 1 activity in serum of breast cancer patients

Benjamin Nisman, Tanir Allweis, Luna Kadouri 1 , Bela Mali 3 , Tamar Hamburger 1 , Mario Baras 4 , Simon Gronowitz 5 ,  and Tamar Peretz 1
  • 1 Department of Oncology, Hadassah and Hebrew University Medical Centre, Jerusalem, Israel
  • 2 Department of Surgery, Hadassah and Hebrew University Medical Centre, Jerusalem, Israel
  • 3 Department of Pathology, Hadassah and Hebrew University Medical Centre, Jerusalem, Israel
  • 4 Department of Social Medicine and Community Health, Hadassah and Hebrew University Medical Centre, Jerusalem, Israel
  • 5 Group of Clinical Virology, Department of Medical Sciences, Uppsala University, Sweden
  • 6 Benjamin Nisman and Tanir Allweis contributed equally to this work.
Benjamin Nisman, Tanir Allweis, Luna Kadouri, Bela Mali, Tamar Hamburger, Mario Baras, Simon Gronowitz and Tamar Peretz


Background: We compared two recently developed immunoassays for serum thymidine kinase 1 (TK1) activity: one manual assay (DiviTum, Biovica®) and one fully automated assay (Liaison, Diasorin®).

Methods: The study included 368 women: 149 healthy blood donors (control), 59 patients with benign breast disease (BBD) and 160 patients with primary breast cancer (BC).

Results: A regression analysis of the Liaison (y) and DiviTum (x) assays for all three groups yielded the equation y=3.93+0.03x (r=0.85, n=368). The r-value in BC was higher than in control and BBD (0.90 vs. 0.81 and 0.64). The correlation between the two assays for TK1 values above the cut-off was higher compared to that below (0.88 and 0.59). Breakdown of the BBD group into subgroups with proliferative and non-proliferative lesions was effective only with the measurement of TK1 with DiviTum assay (p=0.03). The TK1 activity determined preoperatively in BC patients with DiviTum and Liaison assays was significantly associated with T-stage (for both p=0.01), presence of vascular invasion (p=0.002 and p=0.02), lack of estrogen receptor (ER) (p=0.001 and p=0.01) and progesterone receptor (PR) (p=0.01 and p=0.03) expression. Only TK1 analyzed with the DiviTum assay was associated with tumor grade and molecular subtype of BC (p=0.02 and p=0.003). Multivariate Cox proportional hazards analyses demonstrated that T-stage, PR status and TK1 activity measured by both methods (DiviTum, RR=3.0, p=0.02 and Liaison, RR=3.1, p=0.01) were independent predictors of disease recurrence.

Conclusions: In spite of differences observed between TK1 activity measured by the DiviTum and Liaison assays, both of them may be used for recurrence prediction in preoperative evaluation of BC patients.

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Clinical Chemistry and Laboratory Medicine ( CCLM) publishes articles on novel teaching and training methods applicable to laboratory medicine. CCLM welcomes contributions on the progress in fundamental and applied research and cutting-edge clinical laboratory medicine. It is one of the leading journals in the field, with an impact factor of over three. CCLM is the official journal of nine national clinical societies and associated with EFLM.