INCREASED EXPRESSION OF OSTEONECTIN AND OSTEOPONTIN, 2 BONE-MATRIX PROTEINS, IN HUMAN BREAST-CANCER

Microcalcifications are a common phenomenon associated with breast can cer and are often the only mammographic sign of a malignant breast dis ease. Although microcalcifications are not restricted to breast cancer and can be also associated with benign lesions, it is noteworthy that they are composed exclusively of hydroxyapatite in breast carcinoma. Hydroxyapatite is the bone-associated phosphocalcic crystal the deposi tion of which in bone tissue requires the coordinated expression of se veral molecules such as osteonectin (OSN) and osteopontin (OPN), synth esized by cells of the osteoblastic lineage. In this study, we evaluat ed the expression of these two bone matrix proteins, using an immunope roxidase technique and specific antibodies, in 79 breast lesions inclu ding 28 benign and 51 cancerous specimens. We found that normal mammar y tissue associated with the lesions examined expressed generally unde tectable or lightly detectable (0 or 1 +) amounts of OSN and OPN (92 a nd 81%, respectively). Benign breast lesions, including fibroadenoma a nd fibrocystic dysplasia, were generally weakly stained (0 or 1 +) wit h both anti-OSN and anti-OPN antibodies (96.4 and 60.7%, respectively) . Interestingly, the majority of both in situ and invasive breast carc inoma lesions showed a strong expression (2+ or 3+) for OSN or OPN (74 .5 and 84.3%, respectively). High expression of these two bone matrix proteins was associated with frequent microcalcification deposition in the lesion. This study is the first extensive study of OSN and OPN ex pression in mammary cancers. Our data suggest that OSN and OPN could p lay a role in the formation of ectopic microcalcifications often assoc iated with breast cancer. It is also tempting to speculate that the ex pression of these two glycoproteins by breast cancer cells play a role in the preferred bone homing of breast metastases.