Cancer-Associated Adipocytes in Human Breast Cancer: an Observational Histopathological Study of Dedifferentiation and Stromal Transition

BACKGROUND:Adipose tissue is a major stromal component of the breast cancer (BC) tumor microenvironment (TME), playing a crucial role in BC progression. Cancer-associated adipocytes (CAAs), located at the invasive tumor front, undergo significant morphological and functional alterations. This observational case-control study investigated the dedifferentiation trajectory of CAAs and its impact on BC progression. METHODS:Paired tumor and distant normal adipose tissues from 20 BC patients were analyzed. Histological and immunohistochemical analyses were performed to assess morphological changes and marker expressions α-SMA, S100A4, and CD36 in CAAs. RESULTS:CAAs exhibited features consistent with dedifferentiation toward a myofibroblast-like phenotype, marked by expressing α-SMA and S100A4, indicators of myofibroblasts and tumor-associated fibroblasts. Metabolically, CAAs showed increased CD36 expression and histological features compatible with augmented lipolysis and were spatially associated with areas of extracellular matrix (ECM) remodeling. Masson's trichrome staining demonstrated augmented pericellular collagen deposition, accompanied by increased tissue stiffness and enhanced angiogenesis at the tumor-adipose boundary. In addition, nuclear translocation of β-catenin in peritumoral adipocytes implicates the Wnt/β-catenin signaling axis as a potential regulator of adipocyte-mesenchymal transition in this context.