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Collagen (XI) alpha-1 chain (COL11A1) is an independent prognostic factor in breast ductal carcinoma in situ

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


Michael S Toss

Islam M Miligy

Kylie L Gorringe

Mohammed A Aleskandarany

Abdulbaqi Alkawaz

Karuna Mittal

Ritu Aneja

Professor of Breast Cancer Pathology


Collagen11A1 (COL11A1) is a fibrillary type collagen constituting a minor component of the extracellular matrix and plays role in tissue tensile strength. Overexpression of COL11A1 expression is associated with aggressive behavior and poor outcome in several human malignancies. In this study, we evaluated the association between COL11A1 expression and clinicopathological parameters of the breast ductal carcinoma in situ (DCIS) and its prognostic value. COL11A1 protein expression was assessed immunohistochemically in a large well-characterized cohort of DCIS including pure (n = 776) and DCIS associated with invasive carcinoma (DCIS-mixed, n = 239). COL11A1 expression was assessed in tumor cells and surrounding stromal cells, and correlated with clinicopathological parameters, immunoprofile and disease outcome. In pure DCIS, high COL11A1 expression was observed in tumor cells and surrounding stromal cells in 25 and 13% of cases, respectively. Higher COL11A1 expression within the stromal cells was associated with hormone receptor negative, HER2 enriched and triple negative molecular subtypes and showed a positive linear correlation with proliferation index, dense tumor infiltrating lymphocytes and hypoxia-inducible factor 1 alpha. COL11A1 expression in tumor and stromal cells was significantly higher in DCIS associated with invasive carcinoma than in pure DCIS, and within the DCIS-mixed cohort, the invasive component showed higher COL11A1 expression than the DCIS component (all, p [less than] 0.0001). Overexpression of stromal COL11A1 was an independent predictor of shorter local recurrence-free interval for all recurrences (HR = 13.2, 95% CI = 6.9–25.4, p [less than] 0.0001) and for invasive recurrences (HR = 11.2, 95% CI = 4.9–25.8, p [les than] 0.0001). When incorporated with other risk factors, stromal COL11A1 provided better patient risk stratification. DCIS with higher stromal COL11A1 expression showed poor outcome even with adjuvant radiotherapy management. In conclusion, overexpression of stromal COL11A1 is associated with invasive recurrence in DCIS and is a potential marker to predict the response to radiotherapy.


Toss, M. S., Miligy, I. M., Gorringe, K. L., Aleskandarany, M. A., Alkawaz, A., Mittal, K., …Rakha, E. A. (2019). Collagen (XI) alpha-1 chain (COL11A1) is an independent prognostic factor in breast ductal carcinoma in situ. Modern Pathology,

Journal Article Type Article
Acceptance Date Mar 29, 2019
Online Publication Date Jun 7, 2019
Publication Date Jun 7, 2019
Deposit Date Apr 1, 2019
Publicly Available Date Dec 8, 2019
Electronic ISSN 1530-0285
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Keywords DCIS; COL11A1; Stromal expression; Recurrence; Radiotherapy
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