Riboflavin carrier protein: A serum and tissue marker for breast carcinoma

We have earlier shown that the estrogen-modulated riboflavin carrier protei n (RCP) first isolated from the chicken egg is evolutionarily conserved in mammals and is elaborated by lactating mammary gland as demonstrated with r at mammary epithelial cells in culture and confirmed by isolation of the vi tamin carrier from bovine milk. In view of several earlier reports that man y milk proteins as well as other estrogen-inducible proteins are up-regulat ed and secreted into circulation in animal models and in women with neoplas tic breast disease, we analyzed serum RCP levels in a double-blind study us ing a specific radioimmunoassay in pre- and post-menopausal women with clin ically diagnosed breast cancer at early and advanced stages of the disease and compared these levels with those in normal age-matched control voluntee rs. Our data reveal that the serum RCP levels in cycling breast cancer pati ents are 3- to 4-fold higher (p < 0.01) than those in their normal counterp arts. This difference in circulatory RCP levels between cancer patients and their age-matched normal counterparts is further magnified to 9-to 11-fold (p < 0.005) at the post-menopausal stage. In addition, there seems to be a good correlation between rising RCP levels and disease progression, since significantly higher RCP concentrations (p < 0.005) are encountered in pati ents with advanced metastasizing breast cancer versus those with early dise ase. Using specific monoclonal antibodies, RCP could be localized immunohis tochemically in the cytoplasm of invading neoplastic cells of lobular and d uctal carcinomas of the breast, indicating that the malignant cells are pro bably the source of the elevated serum RCP levels in breast cancer. These f indings suggest that measurement of circulatory RCP and the immunohistochem ical staining pattern of RCP in biopsy specimens could be exploited as an a dditional marker in diagnosis/prognosis of breast cancer in women. (C) 2001 Wiley-Liss, Inc.