Plasma Levels and Diagnostic Utility of M-CSF, MMP-2 and its Inhibitor TIMP-2 in the Diagnostics of Breast Cancer Patients

Abstract

Background: M-CSF, MMP-2 and its inhibitor TIMP-2 may play a role in the pathogenesis and proliferation of breast cancer (BC). In this paper, plasma levels and the diagnostic utility of these parameters were investigated in comparison to CA 15-3 in patients with BC and in relation to the control groups: patients with benign breast tumor and healthy subjects.

Methods: Plasma levels of the tested parameters were determined using immunoenzyme assay (ELISA) and CA 15-3 with a chemiluminescence method (CMIA).

Results: Our results demonstrated significant differences in the concentration of the tested parameters and CA 15-3 between BC patients and healthy subjects or benign breast tumor patients. Only the plasma levels of TIMP-2 were significantly higher at all tumor stages (I - IV) when compared to healthy controls. M-CSF and TIMP-2 values were comparable to CA 15-3 values for the diagnostic sensitivity, specificity, the predictive values of positive and negative test results (PPV, NPV) and the area under the ROC curve (AUC) in the total BC group. The combined use of the tested parameters with CA 15-3 resulted in the increase in sensitivity, NPV, and AUC, especially in the combination of M-CSF with comparative tumor marker (78%;65%;0.866, respectively) and TIMP-2 with comparative tumor marker (84%;71%;0.895, respectively).

Conclusions: These findings suggest the usefulness of the tested parameters in the diagnosis of BC. However, the highest usefulness in the diagnostics of early BC (stage I and II) was found in case of TIMP-2 (particularly for differential diagnosis between BC and benign breast tumor) and M-CSF, especially with CA 15-3, which could be a new diagnostic panel.