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.