title: Serum thymidine kinase 1 activity in breast cancer.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Oncology, Hadassah and Hebrew University Medical Centre, Jerusalem, Israel. nisman@hadassah.org.il
authors.forename: Benjamin
authors.initials: B
authors.lastname: Nisman
authors.forename: Tanir
authors.initials: T
authors.lastname: Allweis
authors.forename: Luna
authors.initials: L
authors.lastname: Kaduri
authors.forename: Bella
authors.initials: B
authors.lastname: Maly
authors.forename: Simon
authors.initials: S
authors.lastname: Gronowitz
authors.forename: Tamar
authors.initials: T
authors.lastname: Hamburger
authors.forename: Tamar
authors.initials: T
authors.lastname: Peretz
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000201:enzymology* / Q000473:pathology; D016022:Case-Control Studies; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000473:pathology; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012307:Risk Factors; D013937:Thymidine Kinase / Q000097:blood*
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013937:Thymidine Kinase; C092717:thymidine kinase 1