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

  • Benjamin Nisman EMAIL logo , Tanir Allweis , Luna Kadouri , Bela Mali , Tamar Hamburger , Mario Baras , Simon Gronowitz and Tamar Peretz
Published/Copyright: July 11, 2012
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 51 Issue 2

Abstract

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.

Keywords: benign breast disease; breast cancer; prediction of recurrence; thymidine kinase 1 activity
Corresponding author: Benjamin Nisman, Department of Oncology, Hadassah and Hebrew University Medical Centre, P.O. Box 12000, Jerusalem 91120, Israel Phone: +972 26776766, Fax: +972 26778841

References

1. Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 1991;19:403–10.10.1111/j.1365-2559.1991.tb00229.xSearch in Google Scholar PubMed

2. Jonat W, Arnold N. Is the Ki-67 labelling index ready for clinical use? Ann Oncol 2011;22:500–2.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000287750700002&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.1093/annonc/mdq732Search in Google Scholar PubMed

3. Sherley JL, Kelly TJ. Regulation of human thymidine kinase during the cell cycle. J Biol Chem 1988;263:8350–8.10.1016/S0021-9258(18)68484-4Search in Google Scholar

4. Welin M, Kosinska U, Mikkelsen NE, Carnrot C, Zhu C, Wang L, et al. Structures of thymidine kinase 1 of human and mycoplasmic origin. Proc Natl Acad Sci USA 2004;101:17970–5.10.1073/pnas.0406332102Search in Google Scholar

5. Gronowitz JS, Källander CF, Diderholm H, Hagberg H, Petterson U. Application of an in vitro assay for serum thymidine kinase: results on viral disease and malignancies in humans. Int J Cancer 1984;33:5–12.10.1002/ijc.2910330103Search in Google Scholar

6. Gronowitz JS, Hagberg H, Källander CF, Simonsson B. The use of serum deoxythymidine kinase as a prognostic marker, and in the monitoring of patients with non-Hodgkin’s lymphoma. Br J Cancer 1983;47:487–95.10.1038/bjc.1983.78Search in Google Scholar

7. Källander CF, Simonsson B, Hagberg H, Gronowitz JS. Serum deoxythymidine kinase gives prognostic information in chronic lymphocytic leukemia. Cancer 1984;54:2450–5.10.1002/1097-0142(19841201)54:11<2450::AID-CNCR2820541123>3.0.CO;2-RSearch in Google Scholar PubMed

8. Hallek M, Wanders L, Strohmeyer S, Emmerich B. Thymidine kinase: a tumor marker with prognostic value for non-Hodgkin’s lymphoma and a broad range of potential clinical applications. Ann Hematol 1992;65:1–5.10.1007/BF01715117Search in Google Scholar PubMed

9. Luoni R, Ucci G, Riccardi A, Gobbi P, Avato FM, Vignale C, et al. Serum thymidine kinase in monoclonal gammopathies. Cancer 1992;69:1368–72.10.1002/1097-0142(19920315)69:6<1368::AID-CNCR2820690611>3.0.CO;2-RSearch in Google Scholar PubMed

10. Musto P, Bodenizza C, Falcone A, D’Arena G, Scalzulli P, Perla G, et al. Prognostic relevance of serum thymidine kinase in primary myelodysplastic syndromes: relationship to development of acute myeloid leukaemia. Br J Haematol 1995;90:125–30.10.1111/j.1365-2141.1995.tb03390.xSearch in Google Scholar

11. Di Raimondo F, Giustolisi R, Lerner S, Cacciola E, O’Brien S, Kantarjian H, et al. Retrospective study of the prognostic role of serum thymidine kinase level in CLL patients with active disease treated with fludarabine. Ann Oncol 2001;12:621–5.10.1023/A:1011138825593Search in Google Scholar PubMed

12. Lewenhaupt A, Ekman P, Eneroth P, Nilsson B. Tumour markers as prognostic aids in prostatic carcinoma. Br J Urol 1990;66:182–7.10.1111/j.1464-410X.1990.tb14900.xSearch in Google Scholar

13. Ekman P, Lewenhaupt A. Serum tumour markers in human prostatic carcinoma. The value of a marker panel for prognostic information. Acta Oncol 1991;30:173–5.10.3109/02841869109092345Search in Google Scholar PubMed

14. O’Neill KL, Hoper M, Odling-Smee GW. Can thymidine kinase levels in breast tumors predict disease recurrence? J Natl Cancer Inst 1992;84:1825–8.10.1093/jnci/84.23.1825Search in Google Scholar PubMed

15. Öhrvik A, Lindh M, Einarsson R, Grassi J, Eriksson S. Sensitive nonradiometric method for determining thymidine kinase 1 activity. Clin Chem 2004;50:1597–606.10.1373/clinchem.2003.030379Search in Google Scholar PubMed

16. Nisman B, Allweis T, Kaduri L, Maly B, Gronowitz S, Hamburger T, et al. Serum thymidine kinase 1 activity in breast cancer. Cancer Biomarkers 2010;7:65–72.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000285457700001&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f310.3233/CBM-2010-0148Search in Google Scholar PubMed

17. Nisman B, Yutkin V, Nechushtan H, Gofrit ON, Peretz T, Gronowitz S, et al. Circulating tumor M2 pyruvate kinase and thymidine kinase 1 are potential predictors for disease recurrence in renal cell carcinoma after nephrectomy. Urology 2010;76:513–7.10.1016/j.urology.2010.04.034Search in Google Scholar PubMed

18. Konoplev SN, Fritsche HA, O’Brien S, Wierda WG, Keating MJ, Gornet TG, et al. High serum thymidine kinase 1 level predicts poorer survival in patients with chronic lymphocytic leukemia. Am J Clin Pathol 2010;134:472–7.10.1309/AJCPHMYT93HUIZKWSearch in Google Scholar PubMed

19. Dupont WD, Page DL. Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med 1985;312:146–51.10.1056/NEJM198501173120303Search in Google Scholar PubMed

20. World Health Organization, The World Health Organization histologic typing of breast tumours (2nd ed.). Am J Clin Pathol 1982;78:806–16.Search in Google Scholar

21. Goldhirsch A, Wood WC, Coates AS, Gelber RD, Thürlimann B, Senn HJ, et al. Strategies for subtypes: dealing with the diversity of breast cancer: highlights of the St. Gallen international expert consensus on the primary therapy of early breast cancer 2011. Ann Oncol 2011;22:1736–47.10.1093/annonc/mdr304http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000293300700008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar PubMed PubMed Central

22. Cheang MC, Chia SK, Voduc D, Gao D, Leung S, Snider J, et al. Ki67 index, HER2 status, and prognosis of patients with luminal B breast cancer. J Natl Cancer Inst 2009;101:736–50.10.1093/jnci/djp082Search in Google Scholar PubMed PubMed Central

23. Cox DR. Regression models and life-tables. J R Stat Soc 1972;34:187–202.10.1111/j.2517-6161.1972.tb00899.xSearch in Google Scholar

24. Ekstrand H, Awad RJ, Källander CF, Gronowitz JS. A sensitive assay for quantification of RT activity, based on the use of carrier bound template and non radioactive product detection, with special reference to HIV isolation. Biotechnol Appl Biochem 1996;23:95–105.10.1111/j.1470-8744.1996.tb00368.xSearch in Google Scholar PubMed

25. Karlström AR, Neumüller M, Gronowitz JS, Källander CF. Molecular forms in human serum of enzymes synthesizing DNA precursors and DNA. Mol Cell Biochem 1990;92: 23–35.10.1007/BF00220716Search in Google Scholar PubMed

26. Gronowitz S. A method and kit for determination of thymidine kinase and use thereof. vol. WO/2006/091158 A1, 2006.Search in Google Scholar

27. Guan H, Sun Y, Zan Q, Xu M, Li Y, Zhou J, et al. Thymidine kinase 1 expression in atypical ductal hyperplasia significantly differs from usual ductal hyperplasia and ductal carcinoma in situ: a useful tool in tumor therapy management. Mol Med Report 2009;2:923–9.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000270569200008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=b7bc2757938ac7a7a821505f8243d9f3Search in Google Scholar

28. Huang S, Lin J, Guo N, Zhang M, Yun X, Liu S, et al. Elevated serum thymidine kinase 1 predicts risk of pre/early cancerous progression. Asian Pac J Cancer Prev 2011;12:497–505.Search in Google Scholar

29. Sakamoto S, Iwama T, Ebuchi M, Tsukada K, Sagara T, Kawasaki T, et al. Increased activities of thymidine kinase isozymes in human mammary tumours. Br J Surg 1986;73:272–3.10.1002/bjs.1800730409Search in Google Scholar PubMed

30. Dupont WD, Page DL, Parl FF, Vnencak-Jones CL, Plummer WD Jr, Rados MS, et al. Long-term risk of breast cancer in women with fibroadenoma. N Engl J Med 1994;331: 10–5.10.1056/NEJM199407073310103Search in Google Scholar PubMed

31. Robertson JF, O’Neill KL, Thomas MW, McKenna PG, Blamey RW. Thymidine kinase in breast cancer. Br J Cancer 1990;62:663–7.10.1038/bjc.1990.352Search in Google Scholar PubMed PubMed Central

32. Donegan WL. Tumor-related prognostic factors for breast cancer. CA Cancer J Clin 1997;47:28–51.10.3322/canjclin.47.1.28Search in Google Scholar PubMed

Received: 2012-03-14
Accepted: 2012-06-18
Published Online: 2012-07-11
Published in Print: 2013-02-01

©2013 by Walter de Gruyter Berlin Boston

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https://doi.org/10.1515/cclm-2012-0162
Keywords for this article
benign breast disease; breast cancer; prediction of recurrence; thymidine kinase 1 activity

Articles in the same Issue

  1. Letters to the Editor
  2. Performance evaluation of three different immunoassays for detection of antibodies to hepatitis B core
  3. Serum homocysteine concentrations in Chinese children with autism
  4. Interchangeability of venous and capillary HbA1c results is affected by oxidative stress
  5. Interference of hemoglobin (Hb) N-Baltimore on measurement of HbA1c using the HA-8160 HPLC method
  6. First human isolate of Mycobacterium madagascariense in the sputum of a patient with tracheobronchitis
  7. Protein S and protein C measurements should not be undertaken during vitamin K antagonist therapy
  8. α2-HS glycoprotein is an essential component of cryoglobulin associated with chronic hepatitis C
  9. An unusual interference in CK MB assay caused by a macro enzyme creatine phosphokinase (CK) type 2 in HIV-infected patients
  10. An automated technique for the measurement of the plasma glutathione reductase activity and determination of reference limits for a healthy population
  11. Is osteopontin stable in plasma and serum?
  12. Evidence-based approach to reducing perceived wasteful practices in laboratory medicine
  13. Masthead
  14. Masthead
  15. Editorials
  16. Testing volume is not synonymous of cost, value and efficacy in laboratory diagnostics
  17. Lessons from controversy: biomarkers evaluation
  18. Commercial immunoassays in biomarkers studies: researchers beware!1)
  19. Trials and tribulations in lupus anticoagulant testing
  20. Reviews
  21. Mass spectrometry: a revolution in clinical microbiology?
  22. Chronic Chagas disease: from basics to laboratory medicine
  23. General Clinical Chemistry and Laboratory Medicine
  24. Shop for quality or quantity? Volumes and costs in clinical laboratories
  25. Minor improvement of venous blood specimen collection practices in primary health care after a large-scale educational intervention
  26. Evaluation of high resolution gel β2-transferrin for detection of cerebrospinal fluid leak
  27. Serum kallikrein-8 correlates with skin activity, but not psoriatic arthritis, in patients with psoriatic disease
  28. Soluble urokinase plasminogen activator receptor (suPAR) in the assessment of inflammatory activity of rheumatoid arthritis patients in remission
  29. Bone mass density selectively correlates with serum markers of oxidative damage in post-menopausal women
  30. Validation of a fast and reliable liquid chromatography-tandem mass spectrometry (LC-MS/MS) with atmospheric pressure chemical ionization method for simultaneous quantitation of voriconazole, itraconazole and its active metabolite hydroxyitraconazole in human plasma
  31. Performance of different screening methods for the determination of urinary glycosaminoclycans
  32. Intestinal permeability and fecal eosinophil-derived neurotoxin are the best diagnosis tools for digestive non-IgE-mediated cow’s milk allergy in toddlers
  33. An internal validation approach and quality control on hematopoietic chimerism testing after allogeneic hematopoietic cell transplantation
  34. Serum levels of IgG antibodies against oxidized LDL and atherogenic indices in HIV-1-infected patients treated with protease inhibitors
  35. Cooperation experience in a multicentre study to define the upper limits in a normal population for the diagnostic assessment of the functional lupus anticoagulant assays
  36. Contribution of procoagulant phospholipids, thrombomodulin activity and thrombin generation assays as prognostic factors in intensive care patients with septic and non-septic organ failure
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  45. Evaluation of the BRAHMS Kryptor® Thyroglobulin Minirecovery Test in patients with differentiated thyroid carcinoma
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