EVIDENCE THAT BREAST-CANCER ASSOCIATED MICRO CALCIFICATIONS ARE MINERALIZED MALIGNANT-CELLS

Microcalcifications are often associated with both benign and malignan t human breast lesions. Around 40% of mammary carcinoma present such e ctopic mineralization and frequently, they are the only mammographic f eature that indicate the presence of a tumoral lesion. Microcalcificat ions associated with breast cancer are usually composed of hydroxyapat ite, the bone specific mineral. The mechanisms responsible for the for mation of such crystals within breast malignant tissue have not been e lucidated. A possible clue could be provided by the recent demonstrati on that breast cancer cells express several bone matrix proteins inclu ding osteonectin, osteopontin and bone sialoprotein (BSP). This latter phospho-protein is involved in the initiation of hydroxyapatite cryst allisation and its expression in breast cancer has been associated to the presence of hydroxyapatite microcalcifications. We examined 10 hum an breast cancer lesions which were characterized by the presence of m icrocalcifications and high expression of BSP. Histological examinatio n of the lesions suggested, in most of the cases, that the microcalcif ications were breast cancer cells which became mineralized. Hydroxyapa tite stained in blue by hematoxylin appears concentrated around single of associated cancer cells. Staining of these tissue sections with 4' ,6 diamidino-2-phenylindole which specifically labels DNA led us to de monstrate that the mineralizated structures contain cells. These data are the first direct demonstration that breast microcalcifications are fossils of cancer cells. The mechanisms for such a phenomenon remain to be demonstrated. We speculate that the high expression of BSP could create an appropriate microenvironment for the crystallisation of cal cium and phosphate into hydroxyapatite.