Breast Microcalcifications - Novel Biomarkers for Breast Tissue Pathology

Gosling, Sarah; Scott, Robert; Greenwood, Charlene; Bouzy, Pascaline; Nallala, Jayakrupakar; Lyburn, Iain; Stone, Nicholas; Rogers, Keith

Abstract

Microcalcifications are a key feature of mammography. Calcium phosphate (hydroxyapatite) microcalcifications are associated with both benign and malignant breast tissue and spectroscopic analysis has previously shown microstructure and chemistry variation between different tissue pathologies. It is well documented that the surrounding tissue microenvironment differs between normal and cancerous cells, notably pH and bicarbonate concentration. In addition, environmental factors can impact the formation mechanisms, and therefore the chemistry, of hydroxyapatite microcalcifications. This study hypothesises that the tissue microenvironment governs the formation mechanisms of hydroxyapatite crystals in breast tissue.

A total of 55 breast calcifications incorporating 3 tissue pathologies (benign – B2, ductal carcinoma in-situ – B5a and invasive – B5b) from archive formalin-fixed paraffin-embedded core needle breast biopsies were analysed using X-ray diffraction. The average distance between lattice discontinuities (coherence length) was determined from 538 diffractograms and crystallite size and non-uniform strain calculated using Williamson-Hall analysis.

Both crystallite size and non-uniform strain were found to increase with malignancy. An increase in crystallite size can be explained by a decreasing carbonate content with increasing malignancy. However, the increase in non-uniform strain is unexpected, but can be rationalised by differential substitution of carbonate into the hydroxyapatite lattice, controlled by the tissue microenvironment. An acidic extracellular pH is a characteristic feature of cancer cells. Our findings support a new hypothesis that pH and bicarbonate concentration can influence hydroxyapatite formation mechanisms through acidic precursors leading to differential carbonate substitutions. These cause measurable changes to the crystal microstructure, which act as novel biomarkers for breast malignancy.

• Journal Article Type: Conference Paper
• Online Publication Date: Dec 6, 2019
• Publication Date: Dec 6, 2019
• Deposit Date: Jun 14, 2023
• Journal: BREAST CANCER RESEARCH
• Print ISSN: 1465-5411
• Publisher: Springer Verlag
• Peer Reviewed: Peer Reviewed
• Volume: 21
• Issue: S1
• Publisher URL: https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-019-1225-x