Increased shedding of soluble fragments of P‐cadherin in nipple aspirate fluids from women with breast cancer

Abstract

Breast cancer, a worldwide disease with increasing incidence, develops from ductal/lobular epithelium. Nipple aspirate fluid (NAF), secreted from the breast ducts and lobules, can be analyzed to assess breast metabolic activity. P-cadherin is frequently over-expressed in high-grade invasive breast carcinomas and has been reported to be an enhancer of migration and invasion of breast cancer cells, being correlated with tumor aggressiveness. The present study analyzed the soluble fragment of P-cadherin in milk, NAF and matched plasma samples of healthy subjects and in women with precancer conditions and breast cancer. Soluble P-cadherin was detected in all plasma and milk samples, and in about 31.3% of NAF samples. The lowest levels of soluble P-cadherin were found in plasma, with no significant difference among NoCancer, PreCancer and Cancer patients. The highest concentration of soluble P-cadherin was detected in milk collected during the first trimester of lactation, significantly with respect to all NAF samples. There were significantly higher levels of soluble P-cadherin in NAF from Cancer patients than those in women with NoCancer and PreCancer (P < 0.0001). Although no significant difference was found between in situ and invasive breast cancer, soluble P-cadherin levels were found at high concentrations in c-erbB-2-positive tumors, showing a positive correlation with disease stage grouping and tumor grade, and an inverse relationship with estrogen/progesterone receptor status. High levels of the soluble fragment of P-cadherin in Cancer NAF suggest its possible release via proteolytic processing, favoring cancer cell detachment from breast duct, and suggesting that measuring soluble P-cadherin in NAF may improve the identification of women with increased breast cancer risk.