Prostate microcalcification crystallography as a marker of pathology

Gosling, Sarah B; Arnold, Emily L; Adams, Lois; Cool, Paul; Geraki, Kalotina; Kitchen, Mark O; Lyburn, Iain D; Rogers, Keith D; Snow, Tim; Stone, Nick; Greenwood, Charlene E

Abstract

Prostate cancer remains the most common male cancer; however, treatment regimens remain unclear in some cases due to a lack of agreement in current testing methods. Therefore, there is an increasing need to identify novel biomarkers to better counsel patients about their treatment options. Microcalcifications offer one such avenue of exploration. Microfocus spectroscopy at the i18 beamline at Diamond Light Source was utilised to measure X-ray diffraction and fluorescence maps of calcifications in 10 µm thick formalin fixed paraffin embedded prostate sections. Calcifications predominantly consisted of hydroxyapatite (HAP) and whitlockite (WH). Kendall's Tau statistics showed weak correlations of 'a' and 'c' lattice parameters in HAP with GG (r τ = − 0.323, p = 3.43 × 10-4 and r τ = 0.227, p = 0.011 respectively), and a negative correlation of relative zinc levels in soft tissue (r τ = − 0.240, p = 0.022) with GG. Negative correlations of the HAP 'a' axis (r τ = − 0.284, p = 2.17 × 10-3) and WH 'c' axis (r τ = − 0.543, p = 2.83 × 10-4) with pathological stage were also demonstrated. Prostate calcification chemistry has been revealed for the first time to correlate with clinical markers, highlighting the potential of calcifications as biomarkers of prostate cancer. Prostate cancer is the most common cancer in men in the UK, accounting for 27% of all new male cancer cases 1. Ten-year survival rates are good (78%), despite significant variation in treatments. Many men with high-risk disease are undertreated, particularly older men and those from low socioeconomic backgrounds 2-5. Similarly, 92-98% of men with low-risk disease are over-treated, for example with radical surgery 2. This impacts overall patient mortality and quality of life 2-4. Current diagnostic and prognostic methods also contribute to differences in treatment, where prostate specific antigen (PSA) testing has a high false positive rate (75%) and is incongruent with MRI results in 15-20% cases 3,4. Given potential undertreatment of high-risk cases, overtreatment of low-risk cases and poor diagnostic test performance, diagnostic and prognostic biomarkers are urgently needed to better inform men of their risks and treatment options and improve clinical outcomes. One such biomarker for prostate cancer may be calcification chemistry. Calcifications are deposits of calcium salts, primarily consisting of hydroxyapatite (HAP, Ca 10 (PO 4) 6 (OH) 2), which have been studied in detail in breast cancer, due to their appearance on mammograms. More recent studies have focussed on exploiting differences in the chemical and crystallographic composition of these deposits to understand the microenvironmental changes and develop novel biomarkers 5,6. Calcifications in the prostate are less well studied, though some evidence is emerging that prostate calcification may be associated with cancer prognosis 7,8. Causes of calcifications in the prostate are many-fold, including urinary retention, historic sexually transmitted diseases, inflammatory conditions and prostate cancer, meaning calcifications appear in normal, benign and malignant prostate tissue and vary in size, morphology and composition 9-11. The exact formation mechanisms of prostate calcification are debated, with both deposition of calcium minerals onto corpora amylacea (amyloid bodies linked to cell degradation) and active deposition by osteoblast-like cells suggested as potential modes of action 7,12. Previous studies have identified calcification across the prostate, in all four prostatic zones: peripheral (PZ), central (CZ),

Citation

Gosling, S. B., Arnold, E. L., Adams, L., Cool, P., Geraki, K., Kitchen, M. O., Lyburn, I. D., Rogers, K. D., Snow, T., Stone, N., & Greenwood, C. E. (2025). Prostate microcalcification crystallography as a marker of pathology. Scientific Reports, 15, Article 14979. https://doi.org/10.1038/s41598-025-98692-8

• Journal Article Type: Article
• Acceptance Date: Apr 14, 2025
• Online Publication Date: Apr 29, 2025
• Publication Date: Apr 29, 2025
• Deposit Date: Apr 29, 2025
• Electronic ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 15
• Article Number: 14979
• DOI: https://doi.org/10.1038/s41598-025-98692-8
• Keywords: Prostate cancer; Calcification; Biomarkers
• Public URL: https://keele-repository.worktribe.com/output/1202198
• Publisher URL: https://www.nature.com/articles/s41598-025-98692-8