Calcification microstructure reflects breast tissue microenvironment

DOI: 10.1007/s10911-019-09441-3

Authors: Sarah Gosling (Cranfield University) , Robert Scott (Cranfield University) , Charlene Greenwood (Keele University) , Pascaline Bouzy (University of Exeter) , Jayakrupakar Nallala (University of Exeter) , Iain D. Lyburn (Gloucestershire Hospitals NHS Foundation Trust) , Nicholas Stone (University of Exeter) , Keith Rogers (Cranfield University)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Journal Of Mammary Gland Biology And Neoplasia , VOL 95

State: Published (Approved)
Published: December 2019
Diamond Proposal Number(s): 12303

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.

Journal Keywords: Hydroxyapatite; Carbonate; Breast Cancer; Calcification; X-ray diffraction

Subject Areas: Biology and Bio-materials


Instruments: I18-Microfocus Spectroscopy

Documents:
s10911-019-09441-3.pdf