Characterization of dolomite and calcite microcalcifications in human breast tissue

Pathological crystallization within soft tissues often yields biominerals with properties differing from those of their geological or synthetic counterparts. Microcalcifications (MCs) are abundant in breast tumors, particularly in non-invasive lesions, such as ductal carcinoma in situ (DCIS). Given the challenge of predicting DCIS progression into invasive cancer, it has been suggested that MCs can be leveraged to inform DCIS prognosis. The predominant type of breast MCs are those containing calcium phosphates (CaP), whose crystal properties are commonly held to correlate with malignancy. Less common are non-CaP minerals, which have received less attention, as they are associated mainly with benign lesions. Here, we conducted a retrospective study of tissue samples collected from patients who were originally diagnosed with DCIS and whose current medical status is known. We examined the elemental composition, morphology, and crystal phases of 398 MCs, aiming to investigate potential correlations between MC crystal properties and the progression of DCIS. Our findings revealed primarily non-CaP MCs, an observation that was likely made possible only by the tissue processing methodology employed, which did not involve harsh conditions. We found that non-CaP MCs were abundant in DCIS lesions, that they exhibited diverse morphologies and sizes, and that they were composed of calcite and dolomite. Dolomite formation in cancer has not been reported previously and may be linked to pH fluctuations in the tumor microenvironment. The small size of DCIS lesions often requires pathologists to use the entire sample, thus reducing the number of samples available for further research. Nonetheless, despite our limited sample size, the observed trend indicated an association of dolomite MCs with DCIS lesions that progressed into invasive cancer over time.