Immunoexpression and Prognostic Significance of Multidrug Resistance Markers in Feline Mammary Carcinomas

• Published in: Journal of comparative pathology 2021-02, Vol.183, p.13-25
• Main Authors: Manoel, Verônica Correia, De Carvalho, Pedro Luis Teles, Govoni, Verônica Mollica, Da Silva, Tereza Cristina, Queiroga, Felisbina Luisa, Cogliati, Bruno
• Format: Article
• Language: English
• Subjects: feline mammary carcinoma; lung resistance protein; metallothionein; P-glycoprotein
• ISSN: 0021-9975; 1532-3129
• DOI: 10.1016/j.jcpa.2020.12.008

Feline mammary carcinomas (FMCs) are commonly characterized by high clinical aggressiveness and poor prognosis. FMCs share many features with the corresponding human disease, allowing the comparative investigation of tumour biology and therapeutic strategies, including multidrug resistance (MDR) mechanisms. Although transporting/binding proteins, including permeability glycoprotein (P-gp), lung resistance protein (LRP) and metallothionein (MT), are frequently associated with tumour aggressiveness and unresponsiveness to chemotherapy in human breast cancer, they have not been analysed in FMCs. We investigated the immunoexpression of P-gp, LRP and MT in FMCs and their correlation with clinicopathological parameters and overall survival (OS) time in 46 FMCs, with a median follow-up period of 289 days. These markers were co-expressed in 85% of tumours. P-gp was expressed in 93.4% of FMCs and was positively associated with tumour grade (P = 0.049). While unequivocally observed in all FMCs, LRP immunoexpression did not correlate with any clinicopathological parameters or OS. Expression of MT was significant in triple-negative basal- and normal-like molecular subtypes of FMCs (P = 0.023). The concurrent expression of MDR proteins indicates the potential existence of chemotherapy resistance-related mechanisms in FMCs. The positive association between P-gp and MT immunoexpression and aggressive phenotypes could open new therapeutic and translational strategies for FMCs.