Microcalcification crystallography as a potential marker of DCIS recurrence

Gosling, Sarah B.; Arnold, Emily L.; Davies, Samantha K.; Cross, Hannah; Bouybayoune, Ihssane; Calabrese, Doriana; Nallala, Jayakrupakar; Pinder, Sarah E.; Fu, Liping; Lips, Esther H.; King, Lorraine; Marks, Jeffrey; Hall, Allison; Grimm, Lars J.; Lynch, Thomas; Pinto, Donna; Stobart, Hilary; Shelley Hwang, E.; Wesseling, Jelle; Geraki, Kalotina; Stone, Nicholas; Lyburn, Iain D.; Greenwood, Charlene; Rogers, Keith D.; PRECISION Consortium, Grand Challenge; Thompson, Alastair; Nik-Zainal, Serena; Sawyer, Elinor J.; Davies, Helen; Futreal, Andrew; Navin, Nicholas; Jonkers, Jos; van Rheenen, Jacco; Behbod, Fariba; Schmidt, Marjanka; Wessels, Lodewyk F.A.; Rea, Daniel; Bhattacharjee, Proteeti; Collyar, Deborah; Verschuur, Ellen; van Oirsouw, Marja

Abstract

Ductal carcinoma in-situ (DCIS) accounts for 20-25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite relative mass, hydroxyapatite and whitlockite crystal maturity and, elementally, sodium to calcium ion ratio. A preliminary predictive model for DCIS to invasive cancer progression was developed from these parameters with an AUC of 0.797. These results provide insights into the differing DCIS tissue microenvironments, and how these impact microcalcification formation. [Abstract copyright: © 2023. The Author(s).]

• Journal Article Type: Article
• Acceptance Date: Apr 14, 2023
• Online Publication Date: Jun 8, 2023
• Publication Date: Jun 8, 2023
• Deposit Date: Jun 12, 2023
• Publicly Available Date: Jun 12, 2023
• Journal: Scientific Reports
• Print ISSN: 2045-2322
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 13
• Issue: 1
• Article Number: 9331
• DOI: https://doi.org/10.1038/s41598-023-33547-8
• Keywords: Crystallography, Tumor Microenvironment, Carcinoma, Intraductal, Noninfiltrating - diagnostic imaging - pathology, Female, Carcinoma, Ductal, Breast - pathology, Neoplasm Recurrence, Local - pathology, Humans, Breast Neoplasms - diagnostic imaging - patho
• Additional Information: Received: 21 September 2022; Accepted: 14 April 2023; First Online: 8 June 2023; : The authors declare no competing interests.