Open AccessRelationship between Circulating Tumor Cells, Blood Coagulation, and Urokinase‐Plasminogen‐Activator System in Early Breast Cancer Patients
Author(s) -
Mego Michal,
Karaba Marian,
Minarik Gabriel,
Benca Juraj,
Sedlácková Tatiana,
Tothova Lubomira,
Vlkova Barbora,
Cierna Zuzana,
Janega Pavol,
Luha Jan,
Gronesova Paulina,
Pindak Daniel,
Fridrichova Ivana,
Celec Peter,
Reuben James M.,
Cristofanilli Massimo,
Mardiak Jozef
Publication year - 2015
Publication title -
the breast journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.533
H-Index - 72
eISSN - 1524-4741
pISSN - 1075-122X
DOI - 10.1111/tbj.12388
Subject(s) - circulating tumor cell , medicine , breast cancer , plasminogen activator , urokinase receptor , cancer , oncology , cancer research , metastatic breast cancer , metastasis , pathology
Cancer is a risk factor for venous thromboembolism ( VTE ) and plasma d‐dimer ( DD ) and tissue factor ( TF ) are established VTE associated markers. Circulating tumor cells ( CTC s) are associated with the risk of VTE in metastatic breast cancer. This study aimed to correlate CTC s, blood coagulation and the urokinase plasminogen activator ( uPA ) system in primary breast cancer ( PBC ) patients. This prospective study included 116 PBC patients treated by primary surgery. CTC s were detected by quantitative RT ‐ PCR assay for expression of epithelial ( CK 19) or epithelial‐mesenchymal transition ( EMT ) genes ( TWIST 1, SNAIL 1, SLUG , ZEB 1, FOXC 2). Plasma DD , TF , uPA system proteins were detected by enzyme‐linked immunosorbent assays, while expressions of uPA system in surgical specimens were evaluated by immunohistochemistry. CTC s were detected in 27.6% patients. Patients with CTC s had a significantly higher mean plasma DD (ng/mL) than those of patients without CTC s (632.4 versus 365.4, p = 0.4). There was no association between plasma TF and CTC s. Epithelial CTC s exhibit higher expression of uPA system genes compared to EMT _ CTC s. Patients with CTC s had higher plasma uPA proteins than those of patients without CTC s; there was no correlation between tissue expression of uPA system, CTC s, DD or TF levels. In multivariate analysis CTC s and patients age were independent factors associated with plasma DD . We found association between plasma DD and CTC s indicating a potential role for activation of the coagulation cascade in the early metastatic process. CTC s could be directly involved in coagulation activation or increased CTC s could be marker of aggressive disease and increased VTE risk.