Abstract
BackgroundBreast cancer is the most frequently diagnosed cancer in women. Intraepithelial lesions (IELs), such as usual ductal hyperplasia (UH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) are risk factors that predict a woman's chance of developing invasive breast cancer. Therefore, a comparative study that establishes an animal model of pre-invasive lesions is needed for the development of preventative measures and effective treatment for both mammary IELs and tumors. The purpose of this study was to characterize the histologic and molecular features of feline mammary IELs and compare them with those in women.MethodsFormalin-fixed, paraffin-embedded specimens (n = 205) from 203 female cats with clinical mammary disease were retrieved from the archives of the Purdue University Animal Disease Diagnostic Laboratory and Veterinary Teaching Hospital (West Lafayette, IN), and the Department of Pathology and Veterinary Clinic, School of Veterinary Medicine (Sassari, Italy). Histologic sections, stained with hematoxylin and eosin (HE), were evaluated for the presence of IELs in tissue adjacent to excised mammary tumors. Lesions were compared to those of humans. Immunohistochemistry for estrogen receptor (ER-alpha), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2/neu) and Ki-67 was performed in IELs and adjacent tumor tissues.ResultsIntraepithelial lesions were found in 57 of 203 (28%) feline mammary specimens and were categorized as UH (27%), ADH (29%), and DCIS (44%). Most IELs with atypia (ADH and DCIS) were associated with mammary cancer (91%), whereas UH was associated with benign lesions in 53% of cases. Feline IELs were remarkably similar to human IELs. No ER or PR immunoreactivity was detected in intermediate-grade or high-grade DCIS or their associated malignant tumors. HER-2 protein overexpression was found in 27% of IELs.ConclusionThe remarkable similarity of feline mammary IELs to those of humans, with the tendency to lose hormone receptor expression in atypical IELs, supports the cat as a possible model to study ER- and PR-negative breast lesions.
Highlights
Breast cancer is the most frequently diagnosed cancer in women
We focused on the bestcharacterized Intraepithelial lesions (IELs) that arise in the terminal duct-lobular units; these included usual ductal hyperplasia (UH), atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS) [5]
This implies that most ER-negative invasive breast carcinomas probably evolved from ER-negative DCIS, both of which represent about 25% of their respective categories
Summary
Breast cancer is the most frequently diagnosed cancer in women. Intraepithelial lesions (IELs), such as usual ductal hyperplasia (UH), atypical ductal hyperplasia (ADH), and ductal carcinoma in situ (DCIS) are risk factors that predict a woman’s chance of developing invasive breast cancer. With the implementation of Detection and evaluation of IELs are used routinely to estimate a woman’s risk of developing breast cancer and to aid physicians in designing optimal therapeutic strategies. It was postulated, based on epidemiological studies, that the risk for breast cancer ranges from 1.5-2, 4-5, and 8-10, respectively, for women diagnosed with UH, ADH, and DCIS [3,4]. Several transplantable or chemically induced rodent models have been developed to study human cancers, including osteosarcoma, melanoma, bladder and intestinal tumors, non-Hodgkin lymphoma and mammary tumors [6] These models lack many aspects of human cancers [7]. An animal model that develops spontaneous mammary tumors that resemble human breast cancer in many aspects is needed [8,9]
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