Prevalence and Classification of Spontaneous Mammary Intraepithelial Lesions in Dogs Without Clinical Mammary Disease

Abstract

Mammary intraepithelial lesions (IELs) are noninvasive epithelial proliferations that include ductal hyperplasia (DH), atypical DH (ADH), and ductal carcinoma in situ (DCIS). In women, IELs are associated with increased risk of invasive breast cancer and form a basis for therapeutic decisions. Similarly, in female dogs, IELs are common in tumor-bearing glands and in non-tumor-bearing glands. To determine the prevalence and types of spontaneous IELs, mammary glands from 108 female dogs without clinical mammary disease were evaluated histologically and immunohistochemically. Within this population, 56 dogs (52%) had at least one type of spontaneous IEL, including DH (49 dogs), ADH (14 dogs), low-grade DCIS (19 dogs), intermediate-grade DCIS (12 dogs), and high-grade DCIS (1 dog). Twenty-one dogs had two or more different IEL types. In 23 of 24 dogs with atypical IELs (ADH or DCIS), immunohistochemical expression was determined for estrogen receptor α (ER-α), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2/neu), and Ki-67. For all markers examined, low-grade DCIS had significantly lower scores than did adjacent nonlesional gland; PR expression was significantly decreased in low-grade DCIS compared to other atypical lesions. Sixty-one lesions were ER-α negative (12 ADH, 36 low-grade DCIS, 13 intermediate-grade DCIS), and no lesions overexpressed HER-2/neu. Based on the dog’s prevalence of spontaneous mammary IELs that precede clinical mammary disease, the remarkable histologic similarity between canine and human IELs, and the loss of ER expression in certain IELs in both species, the dog shows promise as a model for human breast preneoplasia.