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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

Authors

Michael S Toss

Islam M Miligy

Kylie L Gorringe

Abdulbaqi Alkawaz

Karuna Mittal

Ritu Aneja

Andrew R Green

Ioannis Roxanis

Emad A Rakha emad.rakha@nuh.nhs.uk



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

Journal Article Type Article
Publication Date Jun 7, 2019
Journal Modern Pathology
Print ISSN 0893-3952
Electronic ISSN 1530-0285
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 32
Pages 1473-1485
APA6 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, 1473-1485. https://doi.org/10.1038/s41379-019-0296-7
DOI https://doi.org/10.1038/s41379-019-0296-7
Keywords DCIS; collagen; poor prognosis; collagen prognostic index recurrence
Publisher URL https://www.nature.com/articles/s41379-019-0296-7

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