Geometric characteristics of collagen have independent prognostic significance in breast ductal carcinoma in situ: an image analysis study

Toss, Michael S; Miligy, Islam M; Gorringe, Kylie L; Alkawaz, Abdulbaqi; Mittal, Karuna; Aneja, Ritu; Ellis, Ian O; Green, Andrew R; Roxanis, Ioannis; Rakha, Emad A

Abstract

Collagen plays a key role in normal and malignant tissue homeostasis. While the prognostic significance of collagen fibre remodeling in invasive breast cancer has been studied, its role in ductal carcinoma in situ (DCIS) remains poorly defined. Using image analysis, we aimed to evaluate the prognostic significance of the geometric characteristics of collagen surrounding DCIS. A large well-characterized cohort of DCIS comprising pure DCIS (n=610) and DCIS co-existing with invasive carcinoma (n=180) were histochemically stained for collagen using picrosirius red. ImageJ software was used to assess collagen density, degree of collagen fibre dispersion and directionality in relation to DCIS ducts’ boundary. We developed a collagen prognostic index and evaluated its prognostic significance. A poor index was observed in 24% of the pure DCIS and was associated with determinants of high-risk DCIS including higher grade, comedo necrosis, hormonal receptor negativity, HER2 positivity and high proliferation index. High index was associated with overexpression of the collagen remodeling protein prolyl-4-hydroxlase alpha 2 and the hypoxia inducible factor 1α. DCIS co-existing with invasive carcinoma had a higher collagen prognostic index than pure DCIS (p

Citation

Toss, M. S., Miligy, I. M., Gorringe, K. L., Alkawaz, A., Mittal, K., Aneja, R., …Rakha, E. A. (2019). Geometric characteristics of collagen have independent prognostic significance in breast ductal carcinoma in situ: an image analysis study. Modern Pathology, 32(10), 1473-1485. https://doi.org/10.1038/s41379-019-0296-7

• Journal Article Type: Article
• Acceptance Date: May 2, 2019
• Online Publication Date: Jun 7, 2019
• Publication Date: Jun 7, 2019
• Deposit Date: May 3, 2019
• Publicly Available Date: Dec 8, 2019
• Journal: Modern Pathology
• Print ISSN: 0893-3952
• Electronic ISSN: 1530-0285
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 32
• Issue: 10
• Pages: 1473-1485
• DOI: https://doi.org/10.1038/s41379-019-0296-7
• Keywords: DCIS; collagen; poor prognosis; collagen prognostic index recurrence
• Public URL: https://nottingham-repository.worktribe.com/output/2018119
• Publisher URL: https://www.nature.com/articles/s41379-019-0296-7