ABSTRACT
In the mid 1800s Trousseau observed cancer-associated thrombosis, of which the underlying pathogenesis still remains unknown. We performed a prospective study on platelet-derived microparticles (PMP) and their procoagulant potential in breast cancer patients. Fifty-eight breast cancer patients and 13 women with benign breast tumors were included in the study. Microparticles (MP) were examined by electron microscopy and FACS analysis using labels for annexin V (total numbers), CD61 (PMP), CD62P and CD63 (activated platelets), CD62E (endothelial cells), CD45 (leukocytes) as well as CD142 (tissue factor). Prothrombin fragment 1+2 (F1+2) and thrombin generation were measured as blood coagulation markers. Numbers of annexin V+-MP were highest in breast cancer patients with larger tumor size (T2; median = 5,637 x 10(6)/l; range = 2,852-8,613) and patients with distant metastases (M1; median = 6,102 x 10(6)/l; range = 3,350-7,445), and differed significantly from patients with in-situ tumor (Tis; median = 3,220 x 10(6)/l; range = 2,277-4,124; p = 0.019), small tumor size (T1; median = 3,281 x 10(6)/l; range = 2,356-4,861; p = 0.043) and women with benign breast tumor (median = 4,108 x 10(6)/l; range = 2,530-4,874; p = 0.040). A total of 82.3% of MP were from platelets, 14.6 % from endothelial cells and 0.3% from leukocytes. Less than 10% of PMP showed degranulation markers. Larger tumor size (T2) and metastases correlated with high counts of PMP and with highest F1+2 levels. Since prothrombin levels and thrombin generation did not parallel MP levels, we speculate that MP act in the microenvironment of tumor tissue and may thus not be an exclusive parameter reflecting in-vivo procoagulant activity.
Subject(s)
Blood Coagulation/physiology , Blood Platelets/pathology , Breast Neoplasms/complications , Thrombosis/complications , Thrombosis/pathology , Adult , Aged , Aged, 80 and over , Blood Platelets/ultrastructure , Case-Control Studies , Endothelial Cells/pathology , Endothelial Cells/ultrastructure , Female , Flow Cytometry , Humans , Leukocytes/pathology , Leukocytes/ultrastructure , Microscopy, Electron , Middle Aged , Neoplasms/complications , Particle Size , Peptide Fragments/metabolism , Prospective Studies , Prothrombin/metabolism , Thrombin/metabolismABSTRACT
BACKGROUND: The aim of the present prospective case-control study was to evaluate the putative relevance of circulating microparticles (MP) as a biomarker in breast cancer patients. MATERIALS AND METHODS: Endothelial cell-(EMP) and leukocyte-derived MP (LMP) were determined by flow cytometry in breast cancer patients (n = 41) and healthy controls (n = 25) and compared to carcinoembryonic antigen (CEA), cancer antigen (CA)15-3 and von Willebrand factor antigen (vWF) levels by specificity-sensitivity profiles. RESULTS: LMP, CEA and CA15-3 levels differed significantly between breast cancer patients and controls, whereas EMP and vWF did not. The specificity-sensitivity profiles of LMP and CA15-3 were similar. CONCLUSION: Increasing levels of circulating LMP (CD45+), CEA and CA15-3 correlated with increasing tumor size, thus reflecting disease stage. LMP showed an equal specificity-sensitivity profile to the established marker CA15-3 and therefore might have the potential to become a new biomarker in breast cancer patients.
