Tissue-based associations of mammographic breast density with breast stem cell markers

Breast Cancer Research

Daniel Visscher¹  Lusine Yaghjyan²  Celine M. Vachon³  Ethan Stoll⁴  Kathleen R. Brandt⁵  Christopher G. Scott⁶  Matthew R. Jensen⁶  Karthik Ghosh⁷ 

[1] Department of Anatomic Pathology, Mayo Clinic College of Medicine;Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida;Department of Health Sciences Research, Division of Epidemiology, Mayo Clinic College of Medicine;Department of Pathology, Immunology and Laboratory Medicine, College of Medicine, University of Florida;Department of Radiology, Mayo Clinic College of Medicine;Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine;Division of General Internal Medicine, Mayo Clinic College of Medicine;

关键词: Breast density;    Stem cell markers;    Breast cancer risk;    Immunohistochemistry;    Staining extent;   

DOI  :  10.1186/s13058-017-0889-3

来源: DOAJ

【 摘 要 】

Abstract Background Mammographic breast density is a well-established, strong breast cancer risk factor but the biology underlying this association remains unclear. Breast density may reflect underlying alterations in the size and activity of the breast stem cell pool. We examined, for the first time, associations of CD44, CD24, and aldehyde dehydrogenase family 1 member A1 (ALDH1A1) breast stem cell markers with breast density. Methods We included in this study 64 asymptomatic healthy women who previously volunteered for a unique biopsy study of normal breast tissue at the Mayo Clinic (2006-2008). Mammographically identified dense and non-dense areas were confirmed/localized by ultrasound and biopsied. Immunohistochemical analysis of the markers was performed according to a standard protocol and the staining was assessed by a single blinded pathologist. In core biopsy samples retrieved from areas of high vs. low density within the same woman, we compared staining extent and an expression score (the product of staining intensity and extent), using the signed rank test. All tests of statistical significance were two-sided. Results A total of 64, 28, and 10 women were available for CD44, CD24, and ALDH1A1 staining, respectively. For all three markers, we found higher levels of staining extent in dense as compared to non-dense tissue, though for CD24 and ALDH1A1 the difference did not reach statistical significance (CD44, 6.3% vs. 2.0%, p < 0.001; CD24, 8.0% vs. 5.6%, p = 0.10; and ALDH1A1, 0.5% vs. 0.3%, p = 0.12). The expression score for CD44 was significantly greater in dense as compared to non-dense tissue (9.8 vs.3.0, p < 0.001). Conclusions Our findings suggest an increased presence and/or activity of stem cells in dense as compared to non-dense breast tissue.

【 授权许可】

Unknown