Protective Effect of HER2 Gene Polymorphism rs24537331 in the Outcome of Canine Mammary Tumors

SIMPLE SUMMARY: Human epidermal growth factor receptor 2 (HER2) participates in breast cancer pathogenesis and progression. However, the role of HER2 in canine mammary tumors is not completely understood, and data from different immunohistochemical studies are conflicting. A remarkable genetic variation of the canine HER2 gene has been recognized, including several single nucleotide polymorphisms (SNPs), which may account for the contradictory results. This study aims to assess the relationship between SNPs rs24537329 and rs24537331 in canine HER2 gene and clinicopathological features, clinical progression, and outcome of canine mammary tumors (CMT). Our results demonstrated that SNP rs24537331 was associated with decreased tumoral necrosis and with longer disease-specific overall survival; however, no significant associations were found between SNP rs24537329 and the tumors’ clinicopathological characteristics or survival. Our data suggest that SNP rs24537331 may have a protective effect in CMT, allowing the identification of a subgroup of animals prone to develop less aggressive forms of the disease. This investigation emphasizes the importance of the animal’s genetic background assessment as a valuable tool to be used by clinicians and oncologists in CMT management. ABSTRACT: The role of HER2 in canine mammary tumors is not completely elucidated, and the contradictory results published so far may be, in part, explained by the genetic variability recognized in the canine HER2 gene. Single nucleotide polymorphism (SNPs) in HER2 were recently associated with less aggressive canine mammary tumor histotypes. This study assesses the relationship between SNPs rs24537329 and rs24537331 in canine HER2 gene and clinicopathological characteristics and outcome of mammary tumors in a group of 206 female dogs. Allelic variants were observed in 69.8% and 52.7% of the dogs for SNP rs24537329 and rs24537331, respectively. Our results demonstrated that SNP rs24537331 was associated with decreased tumoral necrosis (HR: 3.09; p = 0.012) and with longer disease-specific overall survival (HR: 2.59; p = 0.013). However, no statistically significant associations were found between SNP rs24537329 and the tumors’ clinicopathological characteristics or survival. Our data suggest that SNP rs24537331 may have a protective effect in canine mammary tumors, allowing the identification of a subgroup of animals prone to develop less aggressive forms of the disease. This study emphasizes the importance of the genetic tests associated with clinical images and histological examinations when assessing CMT outcomes.