Characterization of the cystic cavities of canine invasive micropapillary mammary carcinoma reveals a complex tumor microenvironment

Invasive micropapillary carcinoma (IMC) of the mammary gland is an aggressive mammary tumor affecting humans, dogs, and other species. This study characterized the cystic cavities and tumor microenvironment in in situ, transitional, and invasive areas of canine IMC, comparing findings to human IMC. Methods included histopathology; histochemistry (PAS, Alcian Blue, Oil Red) for basement membrane and secretion assessment; immunohistochemistry and immunofluorescence for myoepithelial markers (p63, calponin-1, smooth muscle myosin, smooth muscle alpha-actin, cytokeratin 14, vimentin) and other proteins for the characterization of neoplastic and tumor environment cells (pancytokeratin, factor VIII, cleaved caspase-3, EMA, collagen IV, E-cadherin, N-cadherin, hormone receptors); and transmission electron microscopy (TEM) for ultrastructural evaluation. Collagen fiber diameters were measured in IMC and normal mammary gland. Results suggest that canine IMC cystic cavities are lined by modified myoepithelial cells resting on a discontinuous or absent basement membrane. Neoplastic epithelial cells express basal markers and a partial epithelial-mesenchymal transition profile, containing mixed mucosubstances and intracellular neutral lipids. Apoptotic epithelial cells were observed at the periphery of transitional micropapillary areas. Cavities contain PAS-positive neutral glycoprotein secretion. The stroma features cancer-associated fibroblasts and heterogeneous collagen fibers, with larger diameters in invasive areas. This study highlights the structural complexity of canine IMC cavities. The similarity between canine and human IMCs underscores the translational potential of the canine model for investigating tumor biology and progression mechanisms.