Histologic characterization of stem cells in mammary epithelium and stroma

It is unknown whether native cells in benign breast tissue mediate risk of cancer.We therefore aimed to identify cell types in benign human mammary tissueimmunohistologically using markers of stemness and differentiation, and toinvestigate their possible associations with clinical risk factors for breast cancer.We found that cells that are integrated in benign epithelium and areimmunoreactive for the stem cell marker ALDH1 are negative for markers ofglandular differentiation, proliferation, and estrogen receptor. High numbers ofthese cells were associated with the risk factors family history of breast cancer,BRCA1/2 carrier status, low parity, and hormone use.Stromal ALDH1+ cells are either spindle-shaped/polygonal (s/p) or round/oval(r/o), and the latter are positive for the contractile protein marker SMMHC.ALDH1+ s/p cells are positive for the stellate cell marker vinculin. Low numbersof these cells were associated with family history, and when negative for the stemcell marker CD44 they were associated with nulliparity. Low numbers ofALDH1+ CD44+ CD24– r/o cells were associated with family history. ALDH1+r/o cells were positively or negatively associated with low parity depending on thepatients' BRCA1/2 status.High numbers of r/o cells that are positive for the mesenchymal stem cellmarker SSEA3 were associated with low parity, family history, and hormone useafter menopause.This study describes novel stromal cells in breast that were associated with riskfactors for breast cancer. If confirmed in independent cohorts, they may be usedfor stratification of women with regard to risk of breast cancer