title: Digital histologic analysis reveals morphometric patterns of age-related involution in breast epithelium and stroma.
abstract: Complete age-related regression of mammary epithelium, often termed postmenopausal involution, is associated with decreased breast cancer risk. However, most studies have qualitatively assessed involution. We quantitatively analyzed epithelium, stroma, and adipose tissue from histologically normal breast tissue of 454 patients in the Normal Breast Study. High-resolution digital images of normal breast hematoxylin and eosin-stained slides were partitioned into epithelium, adipose tissue, and nonfatty stroma. Percentage area and nuclei per unit area (nuclear density) were calculated for each component. Quantitative data were evaluated in association with age using linear regression and cubic spline models. Stromal area decreased (P = 0.0002), and adipose tissue area increased (P < 0.0001), with an approximate 0.7% change in area for each component, until age 55 years when these area measures reached a steady state. Although epithelial area did not show linear changes with age, epithelial nuclear density decreased linearly beginning in the third decade of life. No significant age-related trends were observed for stromal or adipose nuclear density. Digital image analysis offers a high-throughput method for quantitatively measuring tissue morphometry and for objectively assessing age-related changes in adipose tissue, stroma, and epithelium. Epithelial nuclear density is a quantitative measure of age-related breast involution that begins to decline in the early premenopausal period.
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, 27599.
authors.forename: Rupninder
authors.initials: R
authors.lastname: Sandhu
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599.
authors.forename: Lynn
authors.initials: L
authors.lastname: Chollet-Hinton
authors.affiliation: Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Kirk
authors.affiliation: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599.
authors.forename: Bentley
authors.initials: B
authors.lastname: Midkiff
authors.affiliation: UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, 27599; Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599; Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC, 27599. Electronic address: troester@unc.edu.
authors.forename: Melissa A
authors.initials: MA
authors.lastname: Troester
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology*; D001940:Breast / Q000473:pathology*; D004848:Epithelium / Q000473:pathology; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008875:Middle Aged; D017154:Stromal Cells / Q000473:pathology
keywords: Age-related involution; Breast epithelium; Breast tissue; Histologic analysis; Morphometry; Stroma