Tumor metastasis involves the dissemination of malignant cells into the basement membrane, and the vascular system contributes to the circulating pool of these markers. In this context, our aim has been focused on the development of a non-invasive score based on degradation of the backbone of
glycosaminoglycans of the extracellular matrix; namely
hyaluronic acid (HA), for the assessment of
metastasis in patients with
breast cancer. HA level was determined by
enzyme-linked
immunosorbent assay; CA 15.3 was determined by microparticle
enzyme immunoassay;
hyaluronidase, N-acetyl-β-D-
glucosaminidase, β-
glucuronidase,
glucuronic acid, and
glucosamine were assayed by standard colorimetric techniques in 217 patients with
breast cancer. Statistical analyses were performed by logistic regression and receiver-operating characteristic analysis curves. The multivariate discriminant analysis selects a score based on absolute values of the six
biochemical markers: metastatic
breast cancer score (MBCS) = [1.04 (Numerical constant) + 0.003 × CA 15.3 (U/l) + 0.001 × HA (ng/ml) + 0.004 ×
hyaluronidase (mg N-acetyl-β-D-
glucosamine/ml/18 h) + 0.001 × N-acetyl-β-D-
glucosaminidase (μmol/ml/min) + 0.026 ×
glucuronic acid (ng/ml) + 0.003 ×
glucosamine (μg/dl)]. This function correctly classified 87 % of metastatic
breast cancer at cut-off value = 0.85 (i.e., great than 0.85 indicates patients with metastatic
breast cancer and less than 0.85 indicates patients with non-metastatic
breast cancer). MBCS is a novel, non-invasive, and simple score which can be applied to discriminate patients with metastatic
breast cancer.