# Stromal collagen IV expression and risk of breast cancer death in ductal carcinoma in situ

**Authors:** Gunilla Rask, Malin Jansson, Johan Svensson, Rebecca Wiberg, Fredrik Wärnberg, Ola Billing, Charlotta Wadsten, Malin Sund

PMC · DOI: 10.1038/s44276-025-00191-w · BJC Reports · 2025-10-21

## TL;DR

High levels of collagen IV in breast tissue are linked to a higher risk of dying from breast cancer after DCIS, and collagen IV promotes movement in some cancer cell types.

## Contribution

This study identifies stromal collagen IV as a novel prognostic marker for breast cancer mortality after DCIS.

## Key findings

- High collagen IV expression correlates with increased odds of breast cancer death (OR 4.27).
- Collagen IV promotes migration in triple-negative breast cancer cells in vitro.
- ER+ and HER2+ cell lines are unaffected by collagen IV in migration assays.

## Abstract

Current treatment for ductal carcinoma in situ (DCIS) of the breast is generic, due to lack of risk stratification tools. We investigate the correlation between expression of collagen IV in the breast and risk of dying of breast cancer. We also explore the effect of collagen IV in vitro.

Tissue microarrays from a cohort of women treated for DCIS who later died from breast cancer (n = 43) or were still alive (n = 119), were analysed for collagen IV by immunohistochemistry. Oestrogen receptor positive (ER+), triple negative and human epidermal growth factor receptor 2 amplified (HER2+) cell lines were cultured with and without collagen IV.

High expression of stromal collagen IV correlated with increased odds of dying of breast cancer (OR 2.50; 95% CI 1.16–5.39). This association remained when adjusting for tumour size, margin status, comedo necrosis and progesterone receptor negativity (PR−) (OR 4.27; 95% CI 1.64–11.1).

Triple negative breast cancer cell lines migrated quicker on collagen IV-coated than on uncoated surfaces. By contrast, collagen IV coating did not affect ER+ and HER2+ cell lines.

Abundance of stromal collagen IV increases risk of dying in breast cancer after DCIS, and collagen IV can promote cell motility in vitro.

## Linked entities

- **Proteins:** vkg (viking)
- **Diseases:** breast cancer (MONDO:0004989), ductal carcinoma in situ (MONDO:0005023), triple negative breast cancer (MONDO:0005494)

## Full-text entities

- **Genes:** EREG (epiregulin) [NCBI Gene 2069] {aka EPR, ER, Ep}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, PGR (progesterone receptor) [NCBI Gene 5241] {aka NR3C3, PR}
- **Diseases:** breast cancer (MESH:D001943), tumour (MESH:D009369), comedo necrosis (MESH:D009336), DCIS (MESH:D002285)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

4 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12540875/full.md

## References

4 references — full list in the complete paper: https://tomesphere.com/paper/PMC12540875/full.md

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Source: https://tomesphere.com/paper/PMC12540875