Dataset Information

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

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?ConclusionsOur findings suggest an increased presence and/or activity of stem cells in dense as compared to non-dense breast tissue.

SUBMITTER: Yaghjyan L

PROVIDER: S-EPMC5576318 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Publications

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

Yaghjyan Lusine L Stoll Ethan E Ghosh Karthik K Scott Christopher G CG Jensen Matthew R MR Brandt Kathleen R KR Visscher Daniel D Vachon Celine M CM

Breast cancer research : BCR 20170829 1

<h4>Background</h4>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.<h4>Methods</h4>We included in this study 64 asymptomatic healthy wom ...[more]

PMID: 28851411

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Project description:PURPOSE:Previous studies of breast tissue gene expression have shown that the extratumoral microenvironment has substantial variability across individuals, some of which can be attributed to epidemiologic factors. To evaluate how mammographic density and breast tissue composition relate to extratumoral microenvironment gene expression, we used data on 121 patients with breast cancer from the population-based Polish Women's Breast Cancer Study. EXPERIMENTAL DESIGN:Breast cancer cases were classified on the basis of a previously reported, biologically defined extratumoral gene expression signature with two subtypes: an Active subtype, which is associated with high expression of genes related to fibrosis and wound response, and an Inactive subtype, which has high expression of cellular adhesion genes. Mammographic density of the contralateral breast was assessed using pretreatment mammograms and a quantitative, reliable computer-assisted thresholding method. Breast tissue composition was evaluated on the basis of digital image analysis of tissue sections. RESULTS:The Inactive extratumoral subtype was associated with significantly higher percentage mammographic density (PD) and dense area (DA) in univariate analysis (PD: P = 0.001; DA: P = 0.049) and in multivariable analyses adjusted for age and body mass index (PD: P = 0.004; DA: P = 0.049). Inactive/higher mammographic density tissue was characterized by a significantly higher percentage of stroma and a significantly lower percentage of adipose tissue, with no significant change in epithelial content. Analysis of published gene expression signatures suggested that Inactive/higher mammographic density tissue expressed increased estrogen response and decreased TGF-? signaling. CONCLUSIONS:By linking novel molecular phenotypes with mammographic density, our results indicate that mammographic density reflects broad transcriptional changes, including changes in both epithelia- and stroma-derived signaling.

Dataset Information

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

Background

Methods

Results

Publications

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

Similar Datasets

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