Immunohistochemical expression of hormonal receptors in normal and neoplastic mammary tissue in the dog

The mammary carcinoma is the most frequent tumor in the women as well as in the bitches. In human medicine, the evaluation of immunohistochemical expression of estrogen receptors (ER) α and β, progesterone receptor (PR) and androgen receptor (AR) is very useful to predict prognosis and response to endocrine therapy. However, in veterinary medicine, there is little knowledge of the role of these elements in canine mammary tumors. Especially, the information concerning the expression and significance of AR are very scant. Moreover, among the canine mammary tumors there are often complex/mixed neoplasm, characterized by neoplastic transformation of myoepithelial cells. These cells are involved in the mammary cancer progression, but to date there are not specific studies about their receptorial assessment. The aim of this work was to verify, in canine mammary tumors, the existence of correlations between biological behaviour and immunohistochemical expression of ERα, ERβ, PR and AR. A group of thirty bitches with mammary neoplasm was included in the study. Clinical and reproductive histories were obtained from their owners. The animals were subjected to physical examination and thoracic X-ray. Clinical staging of tumors was carried out according to criteria of WHO. Partial or total mastectomy was performed and the whole tissue, fixed in buffered neutral formalin, was sent to Laboratory of Animal Pathology - University of Camerino (Italy). The animals were followed during a year after the surgery. The plan of follow up included clinical examination and thoracic X-ray. Thirty-two tumors were collected and examined. Histological classification and grading were carried out according to criteria of WHO. The immunohistochemical expression of ERα, ERβ, PR and AR was assessed for each sample. Statistical analysis was performed by Student's t-test and Spearman's correlation. We found specific nuclear reaction against all the receptors in normal and neoplastic epithelial and myoepithelial cells. Only the immunodetection of ERα was higher in young bitches (p minus 0,05) whereas the expression of all the other receptors was not correlated with the age. There were not correlations between receptorial assessment and reproductive variables. The expression of every receptor was higher in normal tissue and benign tumors than in malignant neoplasm. Among malignancies, the lowest levels of every receptors were detected in high grade carcinomas (p minus 0,01). Levels of ERα and PR were inversely correlated with the presence of regional (p minus 0,01) and/or distant (p minus 0,05) metastasis. A lower expression of ERβ was found in carcinomas with nodal positive status (p minus 0,05) whereas a high level of AR seemed weakly correlated with development of distant metastasis (pmajor0,05). A high expression of ERα and/or PR appeared as a good prognostic factors for the DFS (p minus 0,01). ERβ also displayed a positive prognostic significance (p minus 0,05). On the other hand, the levels of AR were inversely correlated only with grading but we showed a slight positive correlation with metastatic power of carcinoma (pmajor0,05). In human breast carcinoma, AR seems to be involved in metastatic development by up-regulation of metalloprotease of matrix (MMP). Therefore, evaluating the correlation among presence of AR, expression of MMP and appearance of distant metastasis also in canine mammary tumors could be very interesting. On the contrary we not found important correlations between the receptorial status of myoepithelial cells and the biological behaviour of tested cases.