Analysis of EGFR and HER-2 expressions in ductal carcinomas in situ in canine mammary glands

Abstract

Biomolecular evidence has shown that ductal carcinoma in situ (DCIS) may develop into invasive carcinoma of the canine mammary gland, and mutations in proto-oncogenes HER2 and EGFR; two members of the family of epidermal growth factor receptors, may be involved in this process. The purpose of this study was the characterization of the immunohistochemical expression of the EGFR and HER2 proteins in the process of neoplastic transformation, supposedly present in ductal carcinomas in situ in canine mammary glands. Fifteen cases of DCIS were evaluated, with a higher expression of HER2 and EGFR being observed in low-grade carcinomas when compared with high-grade neoplasms, and with a high positive statistical correlation in the latter. Results suggest that aggressive tumors tend to lose the expression of EGFR and HER2 simultaneously. The loss of the expression of these markers may be related to the process of neoplastic progression in canine mammary tumors. Keywords: dog, neoplasm, immunohistochemistry, EGFR, CerbB2 RESUMO Evidências biomoleculares sugerem que o carcinoma ductal in situ (CDIS) pode progredir para carcinoma invasor na mama canina e que mutações nos proto-oncogenes HER-2 e EGFR, dois membros da família de receptores para fatores de crescimento epidérmicos, podem estar envolvidas neste processo. A partir disso, este trabalho teve por objetivo caracterizar a expressão imuno-histoquímica das proteínas EGFR e HER-

HER-2, EGFR, Cox-2 and Ki67 expression in lymph node metastasis of canine mammary carcinomas: Association with clinical-pathological parameters and overall survival

“…Furthermore, the frequency of EGFR expression did not differ between primary mammary carcinomas with lymph node metastasis and without metastasis. EGFR expression has been suggested to be an early event in the carcinogenesis of canine mammary carcinoma, which could explain the findings of the present study (Bertagnolli et al, 2011;Ferreira et al, 2012;Silva et al, 2014). However, an association between the positivity to EGFR and the presence of lymph node metastasis was observed by Guimarães et al (2014) but not by Gama et al (2009).…”

Comparative Analysis of the Development of Acquired Radioresistance in Canine and Human Mammary Cancer Cell Lines

“…HER2 protein overexpression has been determined to be both predictive for tumor response to HER2-targeted treatments and prognostic for disease outcome in human patients ( 93 ). Several studies have suggested that ~35% of malignant CMT have either HER2 gene or protein expression ( 94 – 97 ) and that HER2 expression is associated with histological grade, proliferation index and tumor size ( 94 , 96 , 98 ). Human and canine genome sequencing has identified significant homology between the HER2 antigens in both species and although further research is needed, results such as these suggest that human-based immunotherapies (e.g., pertuzumab or trastuzumab) or human developed tyrosine kinase inhibitors, could be successfully employed in HER2 + CMT ( 99 ).…”

Current biomarkers of canine mammary tumors

“…In veterinary medicine, a positive correlation between HER-2 serum (determined by ELISA) and tissue (determined by IHC) expression was noticed [ 71 ]. There is also a positive correlation between HER-2 expression and tumor mitotic index, high histological grade and size [ 72 , 74 , 78 ]. It is considered to be a marker of poor prognosis [ 70 , 73 ].…”