Radiological, Histological and Chemical Analysis of Breast Microcalcifications: Diagnostic Value and Biological Significance

Abstract

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.

Can microcalcifications' characteristics predict the risk of breast cancer metastasis to bone?

“…Our results clearly indicate that elemental composition, but not morphological appearance, of breast microcalcifications can predict the presence or development of bone metastatic lesions. In particular, according with the data reported by Bonfiglio et al [15] , in this study the breast cancer lesions of BM+ patients were frequently characterized by the presence calcifications made of MgHAp. Thus, the presence of MgHAp could play an active role in breast cancer progression.…”

“…In the last years, numerous studies highlighted the role of breast microcalcifications in the pathophysiogenesis of both breast cancer occurrence and progression [3][4][5][6]15,16] . In particular, we recently demonstrated the presence of breast cancer cells with an osteoblast phenotype (breast osteoblast-like cells- BOLCs) able to product microcalcifications made of HA or MgHAp [7] .…”

Programmed death ligand 1 expression in prostate cancer cells is associated with deep changes of the tumor inflammatory infiltrate composition

“…Reports showing a positive correlation between PTX3 expression and poor prognosis in specific human tumors suggest that the role of PTX3 may be very dependent on tissue, cancer type and from the cellular source [62][63][64]. Our results showed an over-expression of PTX3 in PCs, compared to BL, suggesting therefore its possible involvement in tumor progression.…”

“…To better characterize the inflammatory response associated with prostatic lesions, it has been investigated the expression of an inflammation-associated molecule: PTX3. Recent studies have shown that PTX3 may have a prooncogenic role in some cancers, including ovary and lung cancer, prostate carcinoma, pancreatic carcinoma, and bone metastasis from breast cancer [61][62][63]. However, some studies report a protective role of PTX3 against cancer [64].…”

Role of Secreted Frizzled-Related Protein 1 in Early Mammary Gland Tumorigenesis and Its Regulation in Breast Microenvironment

“…Most breast calcifications visible at mammography are made of a combination of calcium and phosphate, the exact composition of the mineral part of bones. Moreover, evidences of osteoblast-like cells in breast tissue suggest a potential for breast cells differentiation in a microcalcification environment [37,[95][96][97][98][99][100][101][102][103]. In 2005, Morgan et al [99] reported that microcalcifications were responsible for increasing the mitogenesis properties of breast cells, resulting in an amplification of the malignant process.…”