Associations of stem cell markers with lobular involution in benign breast tissue.
Academic Article
Overview
abstract
BACKGROUND: Terminal duct lobular unit (TDLU) involution has been linked to decreased breast cancer (BCa) risk in some studies. Whether the number/activity of breast stem cells (SCs) in non-cancerous tissue may influence TDLU involution is unknown. We examined the associations of CD44, CD24, and ALDH1A1 SC markers with TDLU involution. METHODS: We included 309 cancer-free women with biopsy-confirmed benign breast disease. Immunohistochemistry (IHC) was performed using tissue microarrays. For each core, IHC expression was assessed using a semi-automated software as % of positively stained cells for each marker. Eight TDLU involution measures were assessed with an established computational pathology algorithm. Generalized linear regression was used to examine the associations of each marker (≥10% vs. <10%) with each TDLU involution measure (log-transformed), adjusted for BCa risk factors. RESULTS: CD44 was positively associated with acini counts per non-adipose tissue area (epithelial: β=0.307, 95% Confidence Interval [CI 0.072,0.542]; stromal: β=0.249 [ 0.005,0.494]) and median acini density (epithelial: β=0.127 [0.025,0.229]; stromal: β=0.143, [0.037,0.249). Epithelial ALDH1A1 was positively associated with median acini density (β=0.161, [0.045, 0.278]) and stromal ALDH1A1 was positively associated with median acini counts per TDLU (β=0.145, [0.018,0.273]). CONCLUSIONS: Higher CD44 and ALDH1A1 expressions in epithelial and stromal regions were associated with lower TDLU involution. IMPACT: We present the first epidemiological evidence on association of SC markers with TDLU involution.
