Correlative imaging reveals physiochemical heterogeneity of microcalcifications in human breast carcinomas
Name
nihms931861.pdf
Description
Accepted version
Size
1.7 MB
Format
Adobe PDF
Checksum (MD5)
4c460067816baec4c6bcd257eeb14c1d
Author(s)
Kunitake, Jennie AMR
Choi, Siyoung
Nguyen, Kayla X
Lee, Meredith M
He, Frank
Sudilovsky, Daniel
Morris, Patrick G
Jochelson, Maxine S
Hudis, Clifford A
Muller, David A
Date Issued
2018
Journal
Journal of Structural Biology
Publisher
Elsevier BV
Version
Author's final manuscript
Abstract
© 2017 Elsevier Inc. 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 the groundwork for establishing MC heterogeneity in the context of breast cancer biology, and could dramatically improve current prognostic models.
MIT Department
Massachusetts Institute of Technology. Department of Civil and Environmental Engineering
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1016/J.JSB.2017.12.002
