Classification of mammary microcalcifications is based on radiological and histological characteristics that are routinely evaluated during the diagnostic path for the identification of breast cancer, or in patients at risk of developing breast cancer. The main aim of this study was to explore the relationship between the imaging parameters most commonly used for the study of mammary microcalcifications and the corresponding histological and chemical properties. To this end, we matched the radiographic characteristics of microcalcifications to breast lesion type, histology of microcalcifications and elemental composition of microcalcifications as obtained by energy dispersive x ray (EDX)-microanalysis. In addition, we investigated the properties of breast cancer microenvironment, under the hypothesis that microcalcification formation could result from a mineralization process similar to that occurring during bone osteogenesis. In this context, breast lesions with and without microcalcifications were compared in terms of the expression of the main molecules detected during bone mineralization (BMP-2, BMP-4, PTX3, RANKL OPN and RUNX2). Our data indicate that microcalcifications classified by mammography as "casting type" are prevalently made of hydroxyapatite magnesium substituted and are associated with breast cancer types with the poorest prognosis. Moreover, breast cancer cells close to microcalcifications expressed higher levels of bone mineralization markers as compared to cells found in breast lesions without microcalcifications. Notably, breast lesions with microcalcifications were characterized by the presence of breast-osteoblast-like cells. In depth studies of microcalcifications characteristics could support a new interpretation about the genesis of ectopic calcification in mammary tissue. Candidating this phenomenon as an integral part of the tumorigenic process therefore has the potential to improve the clinical management of patients early during their diagnostic path.
Keywords: BMPs; Breast cancer; Casting type; Microcalcifications; Osteoblast-like cells; PTX3; RANKL; RUNX2.