Correlative imaging reveals physiochemical heterogeneity of microcalcifications in human breast carcinomas

© 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 electr...

Full description

Bibliographic Details
Main Authors: 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, Fratzl, Peter, Fischbach, Claudia, Masic, Admir, Estroff, Lara A
Other Authors: Massachusetts Institute of Technology. Department of Civil and Environmental Engineering
Format: Article
Language:English
Published: Elsevier BV 2021
Online Access:https://hdl.handle.net/1721.1/135775
_version_ 1826200917345566720
author 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
Fratzl, Peter
Fischbach, Claudia
Masic, Admir
Estroff, Lara A
author2 Massachusetts Institute of Technology. Department of Civil and Environmental Engineering
author_facet Massachusetts Institute of Technology. Department of Civil and Environmental Engineering
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
Fratzl, Peter
Fischbach, Claudia
Masic, Admir
Estroff, Lara A
author_sort Kunitake, Jennie AMR
collection MIT
description © 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.
first_indexed 2024-09-23T11:43:45Z
format Article
id mit-1721.1/135775
institution Massachusetts Institute of Technology
language English
last_indexed 2024-09-23T11:43:45Z
publishDate 2021
publisher Elsevier BV
record_format dspace
spelling mit-1721.1/1357752023-09-28T19:31:53Z Correlative imaging reveals physiochemical heterogeneity of microcalcifications in human breast carcinomas 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 Fratzl, Peter Fischbach, Claudia Masic, Admir Estroff, Lara A Massachusetts Institute of Technology. Department of Civil and Environmental Engineering © 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. 2021-10-27T20:29:14Z 2021-10-27T20:29:14Z 2018 2020-05-28T18:41:34Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/135775 en 10.1016/J.JSB.2017.12.002 Journal of Structural Biology Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier BV PMC
spellingShingle 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
Fratzl, Peter
Fischbach, Claudia
Masic, Admir
Estroff, Lara A
Correlative imaging reveals physiochemical heterogeneity of microcalcifications in human breast carcinomas
title Correlative imaging reveals physiochemical heterogeneity of microcalcifications in human breast carcinomas
title_full Correlative imaging reveals physiochemical heterogeneity of microcalcifications in human breast carcinomas
title_fullStr Correlative imaging reveals physiochemical heterogeneity of microcalcifications in human breast carcinomas
title_full_unstemmed Correlative imaging reveals physiochemical heterogeneity of microcalcifications in human breast carcinomas
title_short Correlative imaging reveals physiochemical heterogeneity of microcalcifications in human breast carcinomas
title_sort correlative imaging reveals physiochemical heterogeneity of microcalcifications in human breast carcinomas
url https://hdl.handle.net/1721.1/135775
work_keys_str_mv AT kunitakejennieamr correlativeimagingrevealsphysiochemicalheterogeneityofmicrocalcificationsinhumanbreastcarcinomas
AT choisiyoung correlativeimagingrevealsphysiochemicalheterogeneityofmicrocalcificationsinhumanbreastcarcinomas
AT nguyenkaylax correlativeimagingrevealsphysiochemicalheterogeneityofmicrocalcificationsinhumanbreastcarcinomas
AT leemeredithm correlativeimagingrevealsphysiochemicalheterogeneityofmicrocalcificationsinhumanbreastcarcinomas
AT hefrank correlativeimagingrevealsphysiochemicalheterogeneityofmicrocalcificationsinhumanbreastcarcinomas
AT sudilovskydaniel correlativeimagingrevealsphysiochemicalheterogeneityofmicrocalcificationsinhumanbreastcarcinomas
AT morrispatrickg correlativeimagingrevealsphysiochemicalheterogeneityofmicrocalcificationsinhumanbreastcarcinomas
AT jochelsonmaxines correlativeimagingrevealsphysiochemicalheterogeneityofmicrocalcificationsinhumanbreastcarcinomas
AT hudisclifforda correlativeimagingrevealsphysiochemicalheterogeneityofmicrocalcificationsinhumanbreastcarcinomas
AT mullerdavida correlativeimagingrevealsphysiochemicalheterogeneityofmicrocalcificationsinhumanbreastcarcinomas
AT fratzlpeter correlativeimagingrevealsphysiochemicalheterogeneityofmicrocalcificationsinhumanbreastcarcinomas
AT fischbachclaudia correlativeimagingrevealsphysiochemicalheterogeneityofmicrocalcificationsinhumanbreastcarcinomas
AT masicadmir correlativeimagingrevealsphysiochemicalheterogeneityofmicrocalcificationsinhumanbreastcarcinomas
AT estrofflaraa correlativeimagingrevealsphysiochemicalheterogeneityofmicrocalcificationsinhumanbreastcarcinomas