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A multi-modal exploration of heterogeneous physico–chemical properties of DCIS breast microcalcifications

Gosling, Sarah; Calabrese, Doriana; Nallala, Jayakrupakar; Greenwood, Charlene; Pinder, Sarah; King, Lorraine; Marks, Jeffery; Pinto, Donna; Lynch, Thomas; Lyburn, Ian D; Shelley Hwang, E. Shelley; PRECISION Consortium, Grand Challenges; Rogers, Keith; Stone, Nicholas

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Doriana Calabrese

Jayakrupakar Nallala

Sarah Pinder

Lorraine King

Jeffery Marks

Donna Pinto

Thomas Lynch

Ian D Lyburn

E. Shelley Shelley Hwang

Grand Challenges PRECISION Consortium

Keith Rogers

Nicholas Stone


Jelle Wesseling
Research Group

Alastair Thompson
Research Group

Serena Nik-Zainal
Research Group

Elinor J. Sawyer
Research Group

Helen Davies
Research Group

Andrew Futreal
Research Group

Nicholas Navin
Research Group

E. Shelley Hwang
Research Group

Jos Jonkers
Research Group

Jacco van Rheenen
Research Group

Fariba Behbod
Research Group

Esther H. Lips
Research Group

Marjanka Schmidt
Research Group

Lodewyk F.A. Wessels
Research Group

Daniel Rea
Research Group

Proteeti Bhattacharjee
Research Group

Hilary Stobart
Research Group

Deborah Collyar
Research Group

Ellen Verschuur
Research Group

Marja van Oirsouw
Research Group


Ductal carcinoma in situ (DCIS) is frequently associated with breast calcification. This study combines multiple analytical techniques to investigate the heterogeneity of these calcifications at the micrometre scale. X-ray diffraction, scanning electron microscopy and Raman and Fourier-transform infrared spectroscopy were used to determine the physicochemical and crystallographic properties of type II breast calcifications located in formalin fixed paraffin embedded DCIS breast tissue samples. Multiple calcium phosphate phases were identified across the calcifications, distributed in different patterns. Hydroxyapatite was the dominant mineral, with magnesium whitlockite found at the calcification edge. Amorphous calcium phosphate and octacalcium phosphate were also identified close to the calcification edge at the apparent mineral/matrix barrier. Crystallographic features of hydroxyapatite also varied across the calcifications, with higher crystallinity centrally, and highest carbonate substitution at the calcification edge. Protein was also differentially distributed across the calcification and the surrounding soft tissue, with collagen and ß-pleated protein features present to differing extents. Combination of analytical techniques in this study was essential to understand the heterogeneity of breast calcifications and how this may link crystallographic and physicochemical properties of calcifications to the surrounding tissue microenvironment.


Gosling, S., Calabrese, D., Nallala, J., Greenwood, C., Pinder, S., King, L., …Stone, N. (2022). A multi-modal exploration of heterogeneous physico–chemical properties of DCIS breast microcalcifications. Analyst, 147(8), 1641-1654.

Journal Article Type Article
Acceptance Date Jan 24, 2022
Publication Date Mar 21, 2022
Publicly Available Date May 30, 2023
Journal Analyst
Print ISSN 0003-2654
Publisher Royal Society of Chemistry
Volume 147
Issue 8
Pages 1641-1654
Public URL
Publisher URL


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