Correlative imaging techniques reveal organic-inorganic compositions of pathological mineral deposits*

Pathological calcification is a wide-spread phenomenon in the human body, in which calcium minerals form in soft tissues and are found in both normal and damaged tissues. One example are microcalcifications (MCs) found in both benign and malignant breast tissue. Breast cancer is screened using mammography based on MC presence and appearance. Little is known, however, about their materials properties and associated organic matrix, or their correlation to breast cancer prognosis. One of the biggest questions regarding MC formation is whether they form by cell-mediated processes or are the result of cell-independent crystallization that is related to necrosis. We have used a combination of histopathology, Raman microscopy, and electron microscopy to image MCs within snap-frozen human breast tissue and have generated micron-scale resolution correlative maps of crystalline phase, trace metals, particle morphology, and organic matrix chemical signatures within high grade ductal carcinoma in situ (DCIS) and invasive cancer. This multimodal methodology lays the groundwork for establishing MC heterogeneity in the context of breast cancer biology, and has the potential to be applied to other pathological minerals, as well as in vitro models of mineralization.