Molecular and functional characterization of estrogen related receptors (ERR) in canine spontaneous mammary neoplasms and their correlation with the histological type, the IHC4 index and the prognosis

Abstract

Many tumors developed in animals, particularly dogs and cats, such as breast cancer, lymphoma, osteosarcoma, skin cancer and central nervous system resemble neoplasms developed in humans, and therefore, recent research value the study of cancer in animals as models for best understanding cancer in humans. Similar to the human species, mammary gland tumors are cancers that most commonly affect the female dog, the dog being considered an important model for studying this disease. About half of canine mammary tumors are malignant. Several studies point to factors with prognostic value in breast cancer in dogs, such as tumor size, histological type, histological grade and lymph node involvement. However, tumors often considered low-grade malignancies have a more aggressive course, resulting in the death of the patient, contrary to common prognostic indicators. Biological samples of breast tumors in female dogs used in this study will be classified according to their histopathologic features, histological grade, and evaluated according to the index IHC4 obtained from a study of immunohistochemical markers estrogen receptor ± (ER ±), receiver progesterone (PR), the HER2 proto-oncogene and the cell proliferation marker Ki67 in human mammary tumors, thus creating a score with prognostic value comparable to human studies. In adition, there will be the evaluation of three tumor suppressor genes, BRCA1, BRCA2, and GATA3, which will better genotypic characterization of breast tumors and its comparison with human breast cancers. The expression and function of a family of receptors related to the estrogen receptor (ERRs), composed of three members, ERR± (NR3B1 or) ERR² (or NR3B2) and ERR³ (NR3B3 or) will be evaluated in canine mammary tumors by immunohistochemical staining, Real-Time PCR and Western blot. Recent studies have pointed ERR± as a potential prognostic marker in human breast cancer, developing a role as regulator of energy metabolism in the neoplastic cell. This project will include in vitro studies with cells derived from normal and tumor breast tissue in order to elucidate the correlation between the pattern of expression of various biomarkers and tumor progression. At last, the standardization of such methodological tools in a canine model of cancer study will allow a better understanding of the molecular alterations found in canine mammary tumors, aiming to facilitate its control in dogs and possibly humans. (AU)