659 Soluble CD44 standard and V6 in serum of breast cancer patients: An indicator for therapy response

Abstract

CD44 splice variants which contain sequences encoded by exon v6 (CD44 v6) seem to be involved in the process of tumor growth and metastasis in some human tumors. Besides cell surface expression, CD44 v6 was also identified in soluble form (sCD44) in the serum. To evaluate the prognostic potential of CD44 serum levels for clinical progression we determined the concentration of CD44 v6 and CD44 standard in sera of 88 breast cancer patients. Sera of tumorectomized, non-metastatic breast cancer patients contained sCD44 v6 and sCD44 std similar to those of healthy blood donors. In contrast, the mean values for sCD44 v6 and std of sera from metastatic breast cancer patients were significantly higher than those of patients with non-disseminated tumor disease. We found no correlation of sCD44 v6 and sCD44 std serum levels to age, tumor grading, disease-free interval, hormone receptor levels and location of metastases (visceral vs. non-visceral) in breast cancer patients. However, sCD44 v6 concentrations correlated with the number of metastatic sites, while those of sCD44 std form did not. The lack of correlation of v6 expression to lactate dehydrogenase (LDH) levels, a marker of tumor load, indicates that high v6 levels reflect rather the metastatic potential of tumor cells than tumor burden. Furthermore, v6 expression correlated with responsiveness to hormone- or chemotherapy: 93% of patients with low v6 serum levels (≤386 ng/ml) responded to therapy, while only 33% of the overexpressing patients responded. Therefore determination of sCD44 v6 serum concentrations may provide a valuable prognostic marker for responsiveness to drug treatment of breast cancer.