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

Abstract

Background: 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.

Methods: 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.

Results: 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.

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