Immunohistochemical expression of P-glycoprotein and breast cancer resistance protein in canine mammary hyperplasia, neoplasia and supporting stroma.

Introduction: Multidrug resistance of neoplastic cells is frequently related to the expression of ABC-transporters like P-glycoprotein (PGP) and breast cancer resistance protein (BCRP). Our study aimed to determine the expression of PGP and BCRP in the components of canine mammary hyperplasia and tumours, comparing it in different histological stages and grades and describing it in the supporting stroma. Materials and Methods: Samples included 47 lobular hyperplasias and 10 benign and 46 malignant tumours, which were classified into histological subtypes, stages (0, carcinomas in situ; I, locally invasive; and II, lymphovascular emboli or regional node metastasis) and grades (I, II and III according to Pe~na et al. Veterinary Pathology, 50, 94-10). Immunohistochemistry with PGP (C494) and BCRP (BXP-21) antibodies was performed. Results: PGP and BCRP were differently expressed by each mammary neoplastic component (luminal epithelial, myoepithelial and mesenchymal) and supporting stroma. Both were significantly higher in luminal cells of carcinomas versus hyperplasias (PGP P 5 0.0055; BCRP P 5 0.0352). BCRP showed a higher expression in luminal cells of simple carcinomas versus complex and mixed carcinomas (P 5 0.0016). Grade II and III carcinomas had a higher PGP luminal expression than grade I (P 5 0.0375). The positivity of stromal fibroblasts was higher in histological stage II versus I carcinomas (PGP P 5 0.0339; BCRP P 5 0.0127) and in histological grades II versus I carcinomas (PGP P 5 0.0343; BCRP P 5 0.0368). Conclusions: Malignant and invasive tumours were more likely to express PGP and/or BCRP in luminal and stromal components, and this expression could be associated with a more aggressive and chemoresistant phenotype.