Affiliations: [a] Department of Oncology, Hadassah and Hebrew University Medical Centre, Jerusalem, Israel | [b] Department of Surgery, Hadassah and Hebrew University Medical Centre, Jerusalem, Israel | [c] Department of Pathology, Hadassah and Hebrew University Medical Centre, Jerusalem, Israel | [d] Group of Clinical Virology, Department of Medical Sciences, Uppsala University, Sweden
Correspondence:
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Corresponding author: Department of Oncology, Hadassah and Hebrew University Medical Centre, P.O. Box 12000, Jerusalem 91120, Israel. Tel.: +972 26776766; Fax: +972 26447836; E-mail: [email protected]
Note: [1] Equal contribution.
Abstract: Aims:Thymidine kinase 1 (TK1) is an enzyme involved in DNA synthesis and an important proliferation marker. We explored the association of preoperative serum TK1 activity with clinicopathological parameters and prognosis in terms of recurrence-free survival (RFS) in breast cancer (BC) patients. Patients and methods:TK1 activity in serum of 120 healthy women and 161 BC patients was measured by quantitative ELISA. Results:Serum TK1 activity in BC patients was significantly higher than in healthy women (P < 0.0001). In BC patients elevated TK1 activity was significantly associated with advanced T stage (P = 0.015), higher grade (P = 0.013), presence of tumor necrosis (P = 0.006), vascular invasion (P = 0.002), and lack of estrogen receptor (ER) and progesterone receptor (PR) expression (P = 0.0004 and P = 0.003). Higher TK1 activity was found in patients with BRCA1/2 mutations compared to those without the mutation (P = 0.004). Multivariate Cox proportional hazards analyses demonstrated that TK1, adjusted for stage, grade, necrosis, ER and PR negativity was retained as an independent predictor of disease recurrence (Hazard Ratio = 3.9, 95%CI 1.3–11.6, P = 0.013). Conclusion:Elevated serum TK1 is an important risk factor indicating a high proliferation potential of tumors at the time of excision. In multivariate analysis TK1 activity was found to be an independent prognostic factor for RFS.
Keywords: Breast cancer, thymidine kinase 1 activity, prediction of recurrence, BRCA1/2 mutation
