Correlative imaging reveals physiochemical heterogeneity of microcalcifications in human breast carcinomas

Publication date: Available online 6 December 2017 Source:Journal of Structural Biology Author(s): Jennie A.M.R. Kunitake, Siyoung Choi, Kayla X. Nguyen, Meredith M. Lee, Frank He, Daniel Sudilovsky, Patrick G. Morris, Maxine S. Jochelson, Clifford A. Hudis, David A. Muller, Peter Fratzl, Claudia Fischbach, Admir Masic, Lara A. Estroff Microcalcifications (MCs) are routinely used to detect breast cancer in mammography. Little is known, however, about their materials properties and associated organic matrix, or their correlation to breast cancer prognosis. We combine histopathology, Raman microscopy, and electron microscopy to image MCs within snap-frozen human breast tissue and generate 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. We reveal the heterogeneity of mineral-matrix pairings, including punctate apatitic particles (<2 µm) with associated trace elements (e.g., F, Na, and unexpectedly Al) distributed within the necrotic cores of DCIS, and both apatite and spheroidal whitlockite particles in invasive cancer within a matrix containing spectroscopic signatures of collagen, non-collagen proteins, cholesterol, carotenoids, and DNA. Among the three DCIS samples, we identify key similarities in MC morphology and distribution, supporting a dystrophic mineralization pathway. This multimodal methodology lays ...
Source: Journal of Structural Biology - Category: Biology Source Type: research

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