Análise histomorfológica, imuno-histoquímica e hibridização cromogênica in situ em lesões mamárias proliferativas ductais de cadelas.

Abstract

The canine mammary gland bears significant pathological lesions similar to the human breast and epithelial lesions can be divided into two major groups: non-neoplastic and neoplastic. Various precursor breast non-neoplastic lesions have been implicated in cancer development: ductal and lobular hyperplasia, ductal and lobular carcinoma in situ, and more recently columnar cell lesions. Recent molecular studies suggest that some canine hyperplasias, particularly those with cytological atypia, represent precursors to, or an early stage in the development of, invasive mammary carcinoma. Thus, the present work aimed to perform objective was to define the pathologic spectrum and analyze the expression of cell cycle related proteins in canine mammary intraepithelial non-neoplastic lesions of mammary specimens of dogs with and without tumor. The histologic review showed that intraepithelial lesions were associated with other mammary tumors in the majority of the cases. These lesions were represented by ductal and lobular hyperplasias and columnar cell alterations. We found a higher prevalence of non-neoplastic atypical lesions with ductal carcinomas in situ and invasive carcinomas, and the expression pattern of cell cycle related proteins was very variable from intraepithelial lesions and the adjacent tumors. Immunohistochemical similarities between human and dog intraepithelial lesions also included, increased expression of the proliferation marker Ki-67 and lack expression of hormonal receptors and EGFR. In contrast to canine mammary cancer, analyses of hyperplastic and columnar lesions presented here did not reveal the presence of HER2 protein alterations. Chromogenic in situ hybridization was successful in three HER2 positive cases of mammary carcinomas, however all neoplastic and associated atypical hyperplasias were absent of gene amplification. Our findings demonstrate that the spontaneous epithelial non-neoplastic mammary lesions are common in dogs and may play an important role in the process of malignant neoplastic transformation. To our knowledge, our study is the first to describe columnar cells lesions in the mammary glands of female dogs and these lesions are pathologically and immunophenotypically similar to those in human breast. We may conclude that the canine species could be the most adequate model for new studies for cancer, due to the morphological and genotypic similarities of human lesions. Prospective studies evaluating the lesions molecular behavior may contribute to a better understanding of these changes in canine mammary cancer development.