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 ...
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 WilliamsonHall 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.