HER-2 AND METALLOPROTEASES IN CANINE MAMMARY TUMORS: EXPRESSION IN SINGLE VERSUS MULTIPLE NODULES AND IN SPECIFIC TUMOR SUBTYPES

Amplification of HER2 occurs in 15-25% of human breast cancers and is associated with an aggressive phenotype. Matrix metalloproteinases (MMPs), a family of zinc-dependent endopeptidases acting to degrade the extracellular matrix, are considered as major critical molecules during metastasis and angiogenesis. Recently, MMP1 and MMP9 induced expression and activation were observed in HER2 overexpressing breast cancer cells. In canine mammary tumors (CMTs) the pathogenetic and prognostic role of HER2 is unclear and different authors have showed controversial results on its expression. MMPs expression has been found to have prognostic significance and to be more expressed in malignant versus benign CMTs. In our study we investigated 130 single and 46 multiple malignant CMTs for HER2 expression by IHC. In addition we studied HER2 in a recently identified carcinoma-and-malignant myoepithelioma subtype. We documented a very low HER2 overexpression (0.8%) with no differences between single versus multiple nodules. Also, luminal and basal tumoral components, including malignant myoepithelium, were not differently expressing HER2. Specific subtypes of HER2-negative CMTs were tested for the IHC expression of MMP2 and MMP9. Luminal cells showed always a higher expression then basal/myoepithelial cells and the stroma was negative. A high MMPs expression was significantly associated with matrix deposition and remodeling in the complex and mixed tumors. These results seem to indicate a non-significant role of HER2 in CMTs development and, by comparison with the literature results, reinforce the need of standardized IHC procedures. In addition, our study shows that MMPs expression in CMTs is strongly influenced by the tumor subtype and this should be taken into consideration for further studies aiming to clarify the role of these peptidases in the canine mammary metastastic process.