Evaluation of the prognostic value of fibrinolytic elements in invasive breast carcinoma patients.

Breast cancer (BrC) is one of the most serious oncological problems in the world. The aim of the study was to evaluate concentrations of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) and their ratios: t-PA/PAI-1 and PAI-1/t-PA in breast cancer patients and in healthy individuals and to estimate the ability of fibrinolytic parameters in predicting neoplasm disease and disease relapse. One hundred and five women were enrolled in the study, including 60 cases with primary BrC, (M0) and 45 healthy females. Follow-up was completed in all BrC patients with a 16.7% recurrence rate. An immunoassay of t-PA, PAI-1 in all cases was made as well as the immunohistochemistry of estrogen and progesterone receptors, human epidermal growth factor receptor 2, E-cadherin, and Ki-67 was performed in BrC subjects. A significantly higher PAI-1 concentration in breast cancer patients below the age of 55 than in controls was obtained. According to the ROC curve analysis, the PAI-1 concentration demonstrates the most accurate prognostic value with the cut-off point at 33.91 ng/ml, with 90% sensitivity and 36% specificity, which discriminates between controls and cancer patients. However, t-PA presents the highest area under the receiver-operating characteristic curves (AUCROC)=0.634 in predicting disease relapse with the cut-off value of 5.3 ng/ml. According to the Kaplan-Meier curves, a high concentration of t-PA (>5 ng/ml) and a lower PAI-1/t-PA ratio (<7.5) are associated with shorter survival. Evaluation of plasma t-PA and PAI-1 concentrations may deliver relevant prognostic information for breast cancer patients.

Heparanase link between vasculogenesis and angiogenesis as well as a predictive factor of a shorter survival rate.

Heparanase concentration is low in normal epithelia cells but its overexpression is reported in many carcinomas, including sarcomas and haematological malignancies. The purpose of this study was to investigate the association with selected angiogenic parameters as well as in the number of circulating endothelial progenitors (EPCs) in respect to low, moderate and high concentrations of heparanase. Also, we estimated the diagnostic usefulness of the heparanase concentration for disease recurrence prediction in breast cancer cases. Eighty-six patients with IA-IIB stage invasive breast carcinoma who passed a comprehensive clinicopathologic evaluation were included in the study. The median tumour diameter was 1.5 cm. Twenty cases showed lymph node metastasis (N1). Follow-up was completed in all patients a median follow-up was 33.5 months with a 11.6% recurrence rate. An immunoassay of selected angiogenic parameters, heparanase, as well as an immunohistochemistry of oestrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2), Ki67 and E-cadherin was performed in all cases. Circulating EPCs were determined by flow cytometry. Higher levels of heparanase in oestrogen and progesterone receptor negative cancers than in positive ones were noted. A higher concentration of heparanase was observed in T2 cases than T1 subjects. Significant positive associations between circulating EPCs, soluble forms of VEGF receptors and increasing plasma levels of heparanase were obtained. Follow-up revealed a significantly higher incidence of disease relapse in breast cancer patients with high baseline concentrations of heparanase. Heparanase was the most accurate biomarker with an AUCROC = 0.72. The cut-off value of 213.74 pg/mL was identified in order to discriminate between disease recurrence patients and those without disease relapse. We suggest, that a high concentration of heparanase next to tumour size and oestrogen and progesterone receptor expression may serve as an indicator of a more an aggressive character of tumour cells and a shorter survival rate.