title: Triple-negative vimentin-positive heterogeneous feline mammary carcinomas as a potential comparative model for breast cancer.
abstract: BACKGROUND
  Human breast cancer is a heterogeneous disease classified by molecular subtyping into luminal A, luminal B, HER2-overexpressing, basal-like, claudin-low and normal-breast like. The routinely applied and standardized immunohistochemical-based surrogates of this classification group together the last three entities as triple-negative breast cancer (TNBCs) that show the most diverse and complex heterogeneity and represent a therapeutic challenge. In the present work 156 feline mammary lesions consisting of feline mammary carcinomas (FMCs), benign neoplasms, and hyperplastic/dysplastic tissues were evaluated histologically and by immunohistochemistry for expression of basal and luminal cytokeratins (CK), vimentin, alpha-smooth muscle actin, calponin, estrogen receptor (ER) alpha (a), and progesterone receptor (PR). Thirty-seven FMCs with 27 matched non-neoplastic controls were also investigated for gene expression of ERa, ER beta, PR, and HER2.
  
  
  RESULTS
  A large group of hormone receptors (HRs)-negative aggressive carcinomas - that did not overexpress HER2 - could be distinguished from the less aggressive (10.8%) and benign (8%) HRs + tumors, that showed bilineage (luminal and myoepithelial) differentiation. Immunohistochemical evaluations of cytoplasmic filaments indicated that HRs- FMCs are vimentin+, CK14+, and CK5_6+ carcinomas that may resemble the TNBCs (basal like/claudin low) described in women. The identification of luminal and myoepithelial progenitors within the mammary ductal system suggested potential cells/sites of origin of these tumors. A diffuse and never previously described CKs/vimentin luminal cell co-expression was detected in the non-neoplastic ducts, indicating a potential bilineage progenitor.
  
  
  CONCLUSIONS
  These results indicate and potentially explain the high incidence of triple-negative, vimentin + aggressive tumors in cats that may used to elucidate some of the challenging features of TNBCs in women.
authors.forename: Diego
authors.initials: D
authors.lastname: Caliari
authors.forename: Valentina
authors.initials: V
authors.lastname: Zappulli
authors.forename: Roberta
authors.initials: R
authors.lastname: Rasotto
authors.forename: Barbara
authors.initials: B
authors.lastname: Cardazzo
authors.forename: Federica
authors.initials: F
authors.lastname: Frassineti
authors.forename: Michael H
authors.initials: MH
authors.lastname: Goldschmidt
authors.forename: Massimo
authors.initials: M
authors.lastname: Castagnaro
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism*; D002371:Cat Diseases / Q000378:metabolism*; D002415:Cats; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D014746:Vimentin / Q000235:genetics / Q000378:metabolism*
chemical_list: D011956:Receptors, Cell Surface; D014746:Vimentin