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Mammographic Density and Matrix Metalloproteinases in Breast Tissue

Content Provider	Springer Nature Link
Author	Steude, Jana S. Maskarinec, Gertraud Erber, Eva Verheus, Martijn Hernandez, Brenda Y. Killeen, Jeffrey Cline, J. Mark
Copyright Year	2009
Abstract	Mammographic density is a strong risk factor for breast cancer, yet the underlying histopathologic correlates are not clear. Matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) play important roles in multiple stages of tumorigenesis. This study examined the association between mammographic density and expression of MMPs 1, 3, 9, and 12 and TIMP3 in benign and malignant breast tissue of 277 women with mainly Caucasian and Japanese ancestry. Tissue microarrays with up to 4 benign and 4 malignant cores per woman were stained immunohistochemically and evaluated. Digitized prediagnostic mammograms were assessed for densities using a computer-assisted method. General linear models adjusted for known confounders were applied to estimate mean densities by staining category. Strong expression of all MMPs was about twice as frequent in malignant as in benign tissue, while TIMP3 expression in stromal tissue was higher in benign than malignant cores. For MMP3 and 9, less than 10% of cores stained positive; thus, they were not further analyzed. None of the markers showed a statistically significant association with breast density in the entire study population and ethnic-specific results were conflicting and difficult to explain. Although not statistically significant, mean density was consistently lower with more extensive TIMP3 expression in stromal and epithelial tissue. These findings indicate that the higher breast cancer risk in women with dense breasts may be influenced by lower TIMP3 expression. However, future investigations into activities and ratios of additional proteases and their inhibitors as well as other pathways, such as inflammation, are needed.
Starting Page	57
Ending Page	65
Page Count	9
File Format	PDF
ISSN	18752292
Journal	Cancer Microenvironment
Volume Number	3
Issue Number	1
e-ISSN	18752284
Language	English
Publisher	Springer Netherlands
Publisher Date	2009-12-10
Publisher Institution	International Cancer Microenvironment Society
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Breast cancer Immunohistochemistry Stroma Mammographic density Ethnicity Biomedicine general Biochemistry Cell Biology Immunology Oncology Cancer Research
Content Type	Text
Resource Type	Article
Subject	Cancer Research Oncology

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