ArticleModern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc2019
Geometric characteristics of collagen have independent prognostic significance in breast ductal carcinoma in situ: an image analysis study.
Article in Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 23 citations in OpenAlex.
- The association between tumor-stromal collagen features and the clinical outcomes of patients with breast cancer: a systematic review.Breast cancer research : BCR · 2025Pooled it
- Whole-slide mapping of tumor tissue fiber architecture via computational scattered light imaging.Biomedical optics express · 2026Article
- Targeting collagen in "armored and cold" tumors: Overcoming barriers to cancer therapy.Cancer pathogenesis and therapy · 2025Review
- Tumor-Associated Macrophages and Collagen Remodeling in Mammary Carcinomas: A Comparative Analysis in Dogs and Humans.International journal of molecular sciences · 2025Article
- Article
- Ion Channel-Extracellular Matrix Interplay in Colorectal Cancer: A Network-Based Approach to Tumor Microenvironment Remodeling.International journal of molecular sciences · 2025Article
- The Microenvironment in DCIS and Its Role in Disease Progression.Advances in experimental medicine and biology · 2025Review
- Comparative evaluation of collagen modifications in breast cancer in human and canine carcinomas.Scientific reports · 2024Article
- Extracellular Microenvironment Alterations in Ductal Carcinoma In Situ and Invasive Breast Cancer Pathologies by Multiplexed Spatial Proteomics.International journal of molecular sciences · 2024Article
- MicroRNA-182-5p Inhibits Hypertrophic Scar Formation by Inhibiting the Proliferation and Migration of Fibroblasts via SMAD4 Pathway.Clinical, cosmetic and investigational dermatology · 2023Article
- Identifying recurrences and metastasis after ductal carcinoma in situ (DCIS) of the breast.Histopathology · 2023Review
- Association of Tumor-Associated Collagen Signature With Prognosis and Adjuvant Chemotherapy Benefits in Patients With Gastric Cancer.JAMA network open · 2021Article
- Development and validation of a collagen signature-based nomogram for preoperatively predicting lymph node metastasis and prognosis in colorectal cancer.Annals of translational medicine · 2021Article
- Collagen Organization in Relation to Ductal CarcinomaCancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2021Article
- Novel quantitative signature of tumor stromal architecture: polarized light imaging differentiates between myxoid and sclerotic human breast cancer stroma.Biomedical optics express · 2020Article
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Authors and funding
10 authors at 4 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Collagen plays a key role in normal and malignant tissue homeostasis. While the prognostic significance of collagen fiber 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 coexisting with invasive carcinoma (n = 180) were histochemically stained for collagen using picrosirius red. ImageJ software was used to assess collagen density, degree of collagen fiber 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 nuclear grade, comedo type necrosis, hormonal receptor negativity, HER2 positivity and high proliferation index. High collagen prognostic index was associated with the collagen remodeling protein prolyl-4-hydroxlase alpha subunit 2 and the hypoxia-related protein hypoxia inducible factor 1α. DCIS coexisting with invasive breast cancer had a higher collagen prognostic index than pure DCIS ( p < 0.0001). High index was an independent poor prognostic factor for DCIS recurrence for all recurrences (HR = 2.3, p = 0.005) and just invasive recurrences (HR = 3.4, p = 0.003). Interaction between collagen prognostic index and radiotherapy showed that the index was associated with poor outcome even with adjuvant radiotherapy ( p = 0.0001). Collagen reorganization around DCIS is associated with poor outcome and provides a potential predictor for disease progression and resistance to radiotherapy. Mechanistic studies are warranted to decipher the underlying mechanisms.
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