Relationship Between Plasma Urokinase-type Plasminogen Activator(uPA) And Plasminogen Activator Inhibitor(PAI-1) Level And Biological Behaviors In The Breast Cancer Patients

Background and ObjectiveUrokinase Plasminogen activator (uPA) is a complex system, including urokinase plasminogen activator uPA; urokinase plasminogen activator receptor uPAR and its inhibitor PAI-1, PAI-2.Tumor invasion and metastasis is a multifactorial process which requires cells to secrete proteolytic enzymes and their inhibitors joint participation. Activative system is involved in these processes.uPA is a serine protease,with secretion in the form of its first non-activity of single-chain zymogen, pro-uPA and cell surface binding uPAR, pro-uPA by plasmin cleavage of role for the active form of uPA. It also could activate a number of growth factors and promote epithelial membrane protein degradation of matrix metalloproteinase (MMP), which allows easy invasion of tumor to organizations. PAI-1 is the main inhibitor of uPA to serine protease inhibitor superfamily. PAI formed with uPA into a stable complex in order to inhibit the activity of uPA form a stable complex and thus inhibit uPA activity. However, higher levels of PAI-1 a higher levels of PAI-1 response to a poorer prognosis, with poor prognosis.In Past study, it had shown that, the breast cancer patients with higher uPA expression have a lower overall survival than the lower ones.Through the detection uPA/PAI-lof lymph node-negative breast cancers found that uPA system is an independent prognostic factor, prognosis similar to the role and status of axillary lymph nodes, and the prognosis is stronger than the ER, PR, and tumor size. There also have researches poined out that uPA levels and estrogen receptor-related, These whose levels are lower than the uPA's which may have larger possibility in ER-negative.In addition, There also have some reported shown that uPA or PAI-1 may equally predictable the effects in the patients with endocrine therapy for breast cancer treatment and other special effects. So far until now, studies on the uPA system, have pointed out that these molecules play an important role in tumor growth, these proteins are lso coujd be the target of cancer treatment which are potential and effective.In view of the detection of plasma uPA and PAI-1 concentration of researches are rare, while studies of the correlation between markers of uPA/PAI-1 with breast cancer immunohistochemical are not clear, therefore this study was designed to detect the expression levels of uPA and PAI-1 in plasma of breast cancer. and the relationship between mutation with the clinicpathological features of breast cancerMaterials and Methods1. Specimen Preparation:Collect morning plasma of the 88 cases of female breast cancer those are treated between march to December 2009 in changhai hospital. Extracted them and then preservated under the conditions of -88℃after extraction,-80℃under the conditions of preservation, all patients had a complete pathological data, In addition establish 40 cases of healthy as a control group. The study are given informed consent.2. Experimental methods:immunohistochemistry were use to detected by ELISA in the concentrations of uPA and PAI-1 in plasma of experimental group and control group populations.3. Statistical analysis:The SPSS 13.0 statistical software for analysis, P<0.05 indicated that the difference has a statistically significant.Results1. In the 88 cases of breast cancer detected in plasma concentration levels of uPA in plasma (4.934±2.718 ng/ml) PAI-1 concentrations (12.644±5.863 ng/ml) were significantly higher than the normal control group.2. The concentration of uPA in plasma.and the tumor size of the breast cancer (P<0.05), histological grade (P<0.01), clinical stage (P<0.01), axillary lymph node metastasis (P <0.05) were positively correlated with and negatively with the patient's age, pathological subtype (P> 0.05); The concentration of PAI-1 in plasma.concentrations and breast cancer tumor size (P<0.05), clinical stage (P<0.01), axillary lymph node metastasis (P<0.01) were positive correlated with and negatively with age, histological type, pathological subtype (P> 0.05);3. the breast cancer patients with ER-positive expression, concentrations of uPA and PAI-1 expression in plasma is higher than the ER-negative patients (P<0.01). The expression of PR status, have no relationship with uPA and PAI-1 concentration in plasma of brease cancer (P> 0.05). breast cancer patients with HER-2 positive, the plasma levels of uPA and PAI-1 in concentration was significantly higher than HER-2 negative patients (P<0.01).4. Breast cancer patients with uPA and PAI-1 in the concentration of the value have a positive correlation (P<0.01).Conclusion Breast cancer patients with high uPA and PAI-1 expression and tumor invasion and metastasis are closely related;the same to the ER status, and HER2 expression; combined detection of malignant breast cancer may help to determine the progress and predict their biological learning behavior.