Circulating 20S Proteasome in Patients with Non-metastasized Breast Cancer

Background: Recent data suggest a role of the ubiquitin proteasome system in various malignancies. In patients with neoplasms, increased extracellular concentrations of circulating 20S proteasome (c-proteasome) have been detected in blood plasma. We tested the hypothesis that the plasma c-proteasome concentration is a biomarker associated with tumor stage and nodal status in patients with the primary diagnosis of non-metastatic breast cancer. Patients and Methods: Venous plasma concentration of 20S proteasome was measured by ELISA technique in 224 non-metastatic breast cancer patients and in 50 healthy volunteers. To assess the relation of proteasome expression to c-proteasome concentration, tumor specimens from 32 patients were immunohistochemically stained for 20S proteasome using an antibody directed against the core subunits of the catalytic domain of the 20S proteasome. Results: The median c-proteasome concentration was higher (p<0.0001) in breast cancer patients (397.5 ng/ml, range: 200-50,000 ng/ml) than in healthy controls (305 ng/ml, range: 140-425 ng/ml). There was no significant correlation between c-proteasome concentration and strength of proteasomal staining in tumor specimens. Neither tumor size, nor nodal status, nor any other prognostically important clinical parameter, including the presence of disseminated tumor cells in the bone marrow, correlated with high c-proteasome concentrations. Conclusion: Circulating proteasome concentrations appear to be higher in patients presenting with primary breast cancer than in healthy controls. Thus, the ubiquitin-proteasome system might represent a potential target in breast cancer treatment.