Comparison of plasma D-dimer and thrombus precursor protein in patients with operable breast cancer as a potential predictor of lymph node metastasis.

Fibrin formation and removal is continuous during the development of malignancy. Plasma D-dimer is indicative of ongoing fibrinolysis, and circulating soluble fibrin polymer [thrombus precursor protein (TpP)] represents thrombogenic activity. We evaluated the relationship between plasma D-dimer and TpP levels with tumor extent and examined the use of these markers as possible predictors of lymph node metastasis in breast cancer. Preoperative plasma levels of D-dimer and TpP were measured in these 120 patients (93 breast cancer, 27 benign breast disease) and 29 healthy controls. Plasma levels of D-dimer in patients with breast cancer were significantly higher than in healthy controls and in those with benign breast disease. Plasma D-dimer levels in patients with breast cancer were found to be significantly increased according to tumor stage. We also observed that plasma levels of D-dimer were higher in patients with lymph node metastasis than in patients without metastasis. In contrast, TpP levels were not significantly different by the tumor stages and lymph node metastasis. In conclusion, increased D-dimer levels in breast cancer may suggest that an ongoing fibrinolysis within breast cancer tissue occurs during tumor progression. Positive D-dimer levels might be useful for identifying metastatic lymph node in patients with operable breast cancer. However, plasma TpP was not found to be a sensitive marker for detecting tumor-associated subclinical coagulopathy.

Platelet microparticles induce angiogenesis in vitro.

Platelet microparticles (PMP) are endogenous substances generated during the coagulation process in a hypercoagulable state. This study demonstrated that PMP promote the proliferation and survival, migration, and tube formation in human umbilical vein endothelial cells (HUVEC). Heat-treated PMP did not significantly decrease the angiogenic activity in HUVEC compared with that of the untreated PMP. Meanwhile when PMP were treated with activated charcoal, a procedure known to remove the lipid growth factors, the angiogenic activity was significantly reduced. These results suggest that the lipid component(s) of the PMP may be major active factor(s) and that protein component(s) may be minor contributor(s). PMP were also shown to augment endothelial progenitor cell differentiation in peripheral blood mononuclear cells. In addition, PMP-stimulated proliferation, chemotaxis and tube formation of the HUVEC was mediated via the Pertussis toxin-sensitive G protein, extracellular signal-regulated kinase and the phosphoinositide 3-kinase pathway. Herein, a new action of PMP was demonstrated to be a potent angiogenic stimulator. It is expected that in pathological states such as a growing tumour, PMP shed from the circulating platelets may reach adequate concentrations and that the elevated levels of PMP could contribute to florid formation of new blood vessels.

Circulating numbers of endothelial progenitor cells in patients with gastric and breast cancer.

Angiogenic factors like VEGF or G-CSF were reported to mobilize endothelial progenitor cells (EPCs) from the bone marrow. These EPCs were shown to be incorporated in the neovessels of developing tumors. Although the concentrations of angiogenic factors in the peripheral blood were reported to be elevated in cancer patients, the number of circulating EPCs has not been previously investigated. In this study, the number of EPCs circulating in the blood in 16 healthy controls and 71 newly diagnosed cancer patients was examined by a culture assay of peripheral blood mononuclear cells. The number of circulating EPCs was not found to be increased in cancer patients, although the plasma levels of VEGF were elevated. It is suggested that VEGF, at concentrations typical of those observed in the blood of cancer patients, does not mobilize EPCs into the peripheral blood.

Plasma levels of D-dimer and soluble fibrin polymer in patients with hepatocellular carcinoma: a possible predictor of tumor thrombosis.

INTRODUCTION: Fibrin formation and removal occurs continuously during the development of malignancy. Moreover, plasma D-dimer is indicative of ongoing fibrinolysis, and soluble fibrin polymer (Thrombus precursor protein, TpP) represents thrombogenic activity. We evaluated the relationship between the levels of plasma D-dimer and TpP and tumor thrombosis in patients with hepatocellular carcinoma (HCC), and examined these markers as possible predictors of tumor thrombus in the portal or the hepatic vein. MATERIALS AND METHODS: Plasma levels of D-dimer and TpP were measured in 66 HCC patients (38 without tumor thrombosis, 28 with tumor thrombosis) and 29 healthy controls, by enzyme immunoassay using an Asserachrom D-Di kit (Diagnostica Stago, France) and a TpP kit (American Biogenetic Sciences, USA). RESULTS: The plasma levels of D-dimer and TpP in HCC patients were found to be significantly higher than those in healthy controls, and these values were also significantly higher in patients with tumor thrombosis than those without tumor thrombosis. Positive D-dimer (>367 ng/ml) correlated weakly with the presence of tumor thrombosis, whereas positive TpP (>5.4 microg/ml) correlated strongly with the presence of tumor thrombosis. By multivariant logistic analysis, positive TpP level was found to be a significant predictor of the presence of tumor thrombosis. In contrast, positive D-dimer level was not found to be a significant predictor for predicting tumor thrombosis. CONCLUSIONS: Increased D-dimer and TpP levels in HCC may suggest that fibrinolysis and coagulation occur continuously during tumor progression. This study shows that a positive TpP level is a predictor of tumor thrombosis in HCC, which suggests that TpP may be useful for identifying tumor thrombus in the portal and hepatic veins.