Immunohistochemical vascular factor expression in canine inflammatory mammary carcinoma

Vet Pathol. 2014 Jul;51(4):737-48. doi: 10.1177/0300985813503568. Epub 2013 Sep 18.

Abstract

Human inflammatory breast carcinoma (IBC) and canine inflammatory mammary carcinoma (IMC) are considered the most malignant types of breast cancer. IMC has similar characteristics to IBC; hence, IMC has been suggested as a model to study the human disease. To compare the angiogenic and angioinvasive features of IMC with non-IMC, 3 canine mammary tumor xenograft models in female SCID mice were developed: IMC, comedocarcinoma, and osteosarcoma. Histopathological and immunohistochemical characterization of both primary canine tumors and xenografts using cellular markers pancytokeratin, cytokeratin 14, vimentin, and α-smooth muscle actin and vascular factors (VEGF-A, VEGF-D, VEGFR-3, and COX-2) was performed. Tumor cell proliferation index was measured by the Ki-67 marker. The xenograft models reproduced histological features found in the primary canine tumor and preserved the original immunophenotype. IMC xenografts showed a high invasive character with tumor emboli in the dermis, edema, and occasional observations of ulceration. In addition, compared with osteosarcoma and comedocarcinoma, the IMC model showed the highest vascular factor expression associated with a high proliferation index. Likewise, IMC xenografts showed higher COX-2 expression associated with VEGF-D and VEGFR-3, as well as a higher presence of dermal lymphatic tumor emboli, suggesting COX-2 participation in IMC lymphangiogenesis. These results provide additional evidence to consider vascular factors, their receptors, and COX-2 as therapeutic targets for IBC.

Keywords: COX-2; SCID mice; canine mammary tumor; immunohistochemistry; inflammatory breast cancer; vascular factors; xenograft.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cyclooxygenase 2 / metabolism
  • Disease Models, Animal*
  • Dog Diseases / metabolism*
  • Dog Diseases / physiopathology*
  • Dogs
  • Female
  • Gene Expression Regulation, Neoplastic / physiology*
  • Heterografts / pathology
  • Heterografts / transplantation
  • Immunohistochemistry / veterinary
  • Intercellular Signaling Peptides and Proteins
  • Mammary Neoplasms, Animal / metabolism*
  • Mammary Neoplasms, Animal / physiopathology*
  • Mice
  • Mice, SCID
  • Peptides / metabolism*

Substances

  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • vascular factor
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2