Microcalcifications are often associated with human mammary lesions, p
articularly with breast carcinomas. To date, the molecular mechanism t
hat leads to the deposition of hydroxyapatite in the mammary tissue ha
s not been elucidated. Bone sialoprotein (BSP) is a glycoprotein the e
xpression of which coincides with the appearance of the first hydroxya
patite crystals during bone development. In this study, we report the
observation that BSP, a bone matrix protein, is expressed in human mam
mary cancer cells. Using an immunoperoxidase technique, we studied the
expression of BSP in 79 breast lesions, including 28 benign and 51 ma
lignant specimens. Two polyclonal antibodies, one directed against int
act human BSP and the other against a synthetic peptide of BSP (residu
es 277-294), were used and gave identical results. Normal mammary glan
ds expressed undetectable or barely detectable amounts of BSP, and the
majority of the benign lesions examined were generally unstained (0)
or weakly stained (1+). Most of the breast carcinoma specimens (around
87%) showed a significant increase (P = 0.0001) in BSP expression. Br
east carcinomas with microcalcifications had the highest immunoreactiv
ity (2+ or 3+) to BSP antibodies. This is the first demonstration that
BSP expression is significantly increased in breast cancer. Expressio
n of BSP by breast cancer cells could play a major role in the deposit
ion of microcalcifications and in the preferred bone homing of breast
cancer cells.