Mammographic density is related to stroma and stromal proteoglycan expression

Abstract

Background: Mammographic density and certain histological changes in breast tissues are both risk factors for breast cancer. However, the relationship between these factors remains uncertain. Previous studies have focused on the histology of the epithelial changes, even though breast stroma is the major tissue compartment by volume. We have previously identified lumican and decorin as abundant small leucine-rich proteoglycans in breast stroma that show altered expression after breast tumorigenesis. In this study we have examined breast biopsies for a relationship between mammographic density and stromal alterations.

Methods: We reviewed mammograms from women aged 50-69 years who had enrolled in a provincial mammography screening program and had undergone an excision biopsy for an abnormality that was subsequently diagnosed as benign or pre-invasive breast disease. The overall mammographic density was classified into density categories. All biopsy tissue sections were reviewed and tissue blocks from excision margins distant from the diagnostic lesion were selected. Histological composition was assessed in sections stained with haematoxylin and eosin, and the expression of lumican and decorin was assessed by immunohistochemistry; both were quantified by semi-quantitative scoring.

Results: Tissue sections corresponding to regions of high in comparison with low mammographic density showed no significant difference in the density of ductal and lobular units but showed significantly higher collagen density and extent of fibrosis. Similarly, the expression of lumican and decorin was significantly increased.

Conclusion: Alteration in stromal composition is correlated with increased mammographic density. Although epithelial changes define the eventual pathway for breast cancer development, mammographic density might correspond more directly to alterations in stromal composition.

Figure 1

Graphs showing the relation between categories of low (1 and 2) and high (4 and 5) mammographic density and collagenous stroma, duct-lobular unit density, lumican and decorin expression. Bars represent the median level within each category. IHC, immunohistochemistry.

Figure 2

Representative tissue sections from breast tissue associated with low (left panels) and high (right panels) mammographic density. Increased collagenous stroma (upper right) and expression of lumican (middle right) and decorin (lower right) is present in breast tissue associated with high mammographic density. H&E sections (upper panels), lumican immunohistochemistry (middle panels), decorin immunohistochemistry (lower panels).