Associations of stem cell markers CD44, CD24 and ALDH1A1 with mammographic breast density in women with benign breast biopsies

Br J Cancer. 2024 Jul;131(2):325-333. doi: 10.1038/s41416-024-02743-2. Epub 2024 Jun 7.

Abstract

Background: We examined associations of CD44, CD24 and ALDH1A1 breast stem cell markers with mammographic breast density (MBD), a well-established breast cancer (BCa) risk factor.

Methods: We included 218 cancer-free women with biopsy-confirmed benign breast disease within the Nurses' Health Study (NHS) and NHSII. The data on BCa risk factors were obtained from biennial questionnaires. Immunohistochemistry (IHC) was done on tissue microarrays. For each core, the IHC expression was assessed using a semi-automated platform and expressed as percent of positively stained cells for each marker out of the total cell count. MBD was assessed with computer-assisted techniques. Generalised linear regression was used to examine the associations of each marker with square root-transformed percent density (PD), absolute dense and non-dense areas (NDA), adjusted for BCa risk factors.

Results: Stromal CD44 and ALDH1A1 expression was positively associated with PD (≥ 10% vs. <10% β = 0.56, 95% confidence interval [CI] [0.06; 1.07] and β = 0.81 [0.27; 1.34], respectively) and inversely associated with NDA (β per 10% increase = -0.17 [-0.34; -0.01] and β for ≥10% vs. <10% = -1.17 [-2.07; -0.28], respectively). Epithelial CD24 expression was inversely associated with PD (β per 10% increase = -0.14 [-0.28; -0.01]. Stromal and epithelial CD24 expression was positively associated with NDA (β per 10% increase = 0.35 [0.2 × 10-2; 0.70] and β per 10% increase = 0.34 [0.11; 0.57], respectively).

Conclusion: Expression of stem cell markers is associated with MBD.

MeSH terms

  • Adult
  • Aldehyde Dehydrogenase / metabolism
  • Aldehyde Dehydrogenase 1 Family* / metabolism
  • Biomarkers, Tumor / metabolism
  • Biopsy
  • Breast / diagnostic imaging
  • Breast / metabolism
  • Breast / pathology
  • Breast Density*
  • Breast Neoplasms / diagnostic imaging
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • CD24 Antigen* / metabolism
  • Female
  • Humans
  • Hyaluronan Receptors* / analysis
  • Hyaluronan Receptors* / metabolism
  • Mammography / methods
  • Middle Aged
  • Retinal Dehydrogenase* / metabolism
  • Stem Cells / metabolism
  • Stem Cells / pathology

Substances

  • CD24 Antigen
  • Hyaluronan Receptors
  • Aldehyde Dehydrogenase 1 Family
  • Retinal Dehydrogenase
  • ALDH1A1 protein, human
  • CD44 protein, human
  • CD24 protein, human
  • Biomarkers, Tumor
  • Aldehyde Dehydrogenase