Gosling, S, Scott, R, Greenwood, C, Bouzy, P, Nallala, J, Lyburn, ID, Stone, N and Rogers, K (2019) Calcification Microstructure Reflects Breast Tissue Microenvironment. Journal of Mammary Gland Biology and Neoplasia, 24 (4). pp. 333-342.

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Abstract

Microcalcifications are important diagnostic indicators of disease in breast tissue. Tissue microenvironments differ in many aspects between normal and cancerous cells, notably extracellular pH and glycolytic respiration. Hydroxyapatite microcalcification microstructure is also found to differ between tissue pathologies, including differential ion substitutions and the presence of additional crystallographic phases. Distinguishing between tissue pathologies at an early stage is essential to improve patient experience and diagnostic accuracy, leading to better disease outcome. This study explores the hypothesis that microenvironment features may become immortalised within calcification crystallite characteristics thus becoming indicators of tissue pathology. In total, 55 breast calcifications incorporating 3 tissue pathologies (benign – B2, ductal carcinoma in-situ - B5a and invasive malignancy - B5b) from archive formalin-fixed paraffin-embedded core needle breast biopsies were analysed using X-ray diffraction. Crystallite size and strain were determined from 548 diffractograms using Williamson-Hall analysis. There was an increased crystallinity of hydroxyapatite with tissue malignancy compared to benign tissue. Coherence length was significantly correlated with pathology grade in all basis crystallographic directions (P < 0.01), with a greater difference between benign and in situ disease compared to in-situ disease and invasive malignancy. Crystallite size and non-uniform strain contributed to peak broadening in all three pathologies. Furthermore, crystallite size and non-uniform strain normal to the basal planes increased significantly with malignancy (P < 0.05). Our findings support the view that tissue microenvironments can influence differing formation mechanisms of hydroxyapatite through acidic precursors, leading to differential substitution of carbonate into the hydroxide and phosphate sites, causing significant changes in crystallite size and non-uniform strain.

Item Type: Article
Additional Information: This is the final published version of the article (version of record). It first appeared online via Springer at https://doi.org/10.1007/s10911-019-09441-3 - please refer to any applicable terms of use of the publisher.
Uncontrolled Keywords: Hydroxyapatite, Carbonate, Breast Cancer, Calcification, X-ray diffraction
Subjects: Q Science > QD Chemistry > QD415 Biochemistry
R Medicine > RC Internal medicine
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Depositing User: Symplectic
Date Deposited: 09 Dec 2019 10:05
Last Modified: 09 Jan 2020 17:01
URI: http://eprints.keele.ac.uk/id/eprint/7335

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