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. 2017 Aug 29;19(1):100.
doi: 10.1186/s13058-017-0889-3.

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

Lusine Yaghjyan  1 , Ethan Stoll  2 , Karthik Ghosh  3 , Christopher G Scott  4 , Matthew R Jensen  4 , Kathleen R Brandt  5 , Daniel Visscher  6 , Celine M Vachon  7
Affiliations

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

Lusine Yaghjyan et al. Breast Cancer Res. .

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.

Keywords: Breast cancer risk; Breast density; Immunohistochemistry; Staining extent; Stem cell markers.

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Conflict of interest statement

Authors’ information

No further information.

Ethical approval and consent to participate

This study was approved by the Mayo Clinic, Rochester and the University of Florida Institutional Review Boards. Written consent was obtained from all participants.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Example of positive and negative staining for CD44
Fig. 2
Fig. 2
Immunohistochemical staining for CD44 (a), CD24 (b), and aldehyde dehydrogenase family 1 member A1 (ALDH1A1) (c) in sections from dense (left) and non-dense (right) areas within the same woman
Fig. 3
Fig. 3
Distribution of staining extent and expression score for CD44, CD24, and aldehyde dehydrogenase family 1 member A1 (ALDH1A1) in tissue samples from mammographically dense and non-dense areas
See this image and copyright information in PMC

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