VEGF-B, VEGF-A, FLT-1, KDR, ERBB2, EGFR, GRB2, RAC1, CDH1 and HYAL-1 Genes Expression Analysis in Canine Mammary Gland Tumors and the Association with Tumor ClinicoPathological Parameters and Dog Breed Assessment

Abstract

Canine mammary gland tumors (CMTs) are one of the most prevalent cancers in dogs and a good model for human breast cancer (BC), however gene expression analysis of CMTs is scarce. Although divergence of genes expression has been found in BC of different human races, no such research of different dog’s breeds has been done. The purpose of this study was to investigate expression of the VEGF-B, VEGF-A, FLT-1, KDR, ERBB2, EGFR, GRB2, RAC1, CDH1 and HYAL-1 genes of canine mammary carcinomas, compare the expression levels with clinicopathological parameters and analyze expression disparities between different breeds. Carcinomas and adjacent tissues were collected from female dogs to perform routine histopathology, immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR). We found that VEGF-B and EGFR genes were overexpressed in the mammary gland carcinomas compared to adjacent tissue. VEGF-B gene expression had associations with different parameters (tumor size, grade, and absence of metastasis). Furthermore, differences in VEGF-B, FLT1, ERBB2, GRB2, RAC1, CDH1 and HYAL-1 genes expression have been found in different breed dogs (German Shepherd, Yorkshire Terrier) and mixed-breed dogs indicating that a dog’s breed could determine a molecular difference, outcome of cancer and should be accounted as a confounding factor in the future gene expression research.