Introduction

Mammary cancer is the most common cancer of intact female dogs. Due to its high incidence and malignancy rate, characterization of biomarkers for clinical use is a priority in veterinary medicine. The aim of this work was to assess the gene expression patterns of eight genes (CCNA2, CCNB2, CHEK2, TTK, TP53, P21, MDM2, and TGFb-1) in canine mammary cancer and their relationships with clinical parameters to verify their feasibility as prognostic markers.

Methods

Eighty-four samples (44 tumoral and 40 non-tumoral) from 40 individuals plus two animals with no history of cancer were studied. Molecular subtypes (Luminal-A and -B, HER-2+ and Triple Negative) were classified by immunohistochemistry. The quantification of gene expression was performed using real-time PCR. Correlations between the results and clinical parameters were assessed statistically, with significance set at p≤0.05. All the procedures were approved by the local ethics committee on animal use (CEUA-23084.000265/2013-53-UFRA).

Results

Differences in gene expression were observed in all the studied genes except TGFb-1. No correlations between gene expression and clinical characteristics were observed except for MDM2 and pseudopregnancy and P21 and 1-year survival. Correlations between molecular subtypes and gene expression levels were observed in CCNA2 and MDM2 (Luminal-types) and TTK (Triple Negative), while CCNB2 and CHEK2 high expression were observed regardless the molecular subtype. In humans, high expression levels of TTK, CHEK2, and CCNA2 are associated with docetaxel, trastuzumab and tamoxifen resistance, respectively.

Conclusion

Our results suggest these genes could be used as prognostic markers, especially when choosing appropriate chemotherapy protocols.

Funding Information

CNPq, CAPES, UFPA, UFRA.