Evaluation of soluble CD44 variants (std, v5 and v6) in patients with primary breast cancer

Introduction: CD44 is a transmembrane adhesion molecule involved in cell-cell and cell-substrate interactions. As a cell surface glycoprotein, CD44 may be shed or released into circulation by proteolytic enzymatic mechanisms. Alternative splicing of CD44 and aberrant levels of soluble CD44 protein in the serum of cancer patients has been correlated to tumor progression and metastasis. In this study we evaluated the clinical value of CD44 serum levels (sCD44) in patients with primary (non metastatic) breast cancer. Material and Methods: Concentrations of the soluble, variable isoforms sCD44std, sCD44v5 and sCD44v6 were determined with a sensitive ELISA and normalized against the total protein concentration (TP). Pre-operative serum samples from 84 patients and 107 healthy blood donors were analyzed. The results were correlated to histo-pathological parameters. Results: Sera of breast cancer patients showed elevated concentrations for sCD44v6 (p=0,0001) and for total protein (p=0,0001), whereas overall sCD44 (sCD44std) and sCD44v5 did not differ. Patients with lymph node metastasis showed elevated sCD44v6 serum concentrations in comparison to patients without lymph node involvement and healthy controls. Furthermore, high sCD44v5- and sCD44v6-concentrations above the 75%-percentile were correlated to large tumor size as well as lymph node metastasis. Conclusion: Our results suggest that soluble CD44v6 is upregulated in breast cancer patients. sCD44v6 seems to play an important role in tumor progression and metastasis in breast cancer. Determination of sCD44v6-concentrations may be helpful to identify subgroups of breast cancer patients with a high risk for lymph node metastasis.