Canine Mammary Tumors: A Review and Consensus of Standard Guidelines on Epithelial and Myoepithelial Phenotype Markers, HER2, and Hormone Receptor Assessment Using Immunohistochemistry

Although there have been several studies on the use of immunohistochemical biomarkers of canine mammary tumors (CMTs) the results are difficult to compare. This paper provides guidelines on the most useful immunohistochemical markers in order to standardize their use and understand how outcomes are measured, thus assuring reproducibility of results. We have reviewed the biomarkers of canine mammary epithelial and myoepithelial cells and identified those which are most useful, as well as those markers for stromal invasion and lymph node micrometastatic disease. A 10% threshold for positive reaction for most of these markers is recommended. Guidelines on immunolabeling for HER2, estrogen receptors (ER) and progesterone receptors (PR) are provided along with the specific recommendations for interpretation of the results for each of these biomarkers in CMTs. Only 3+ HER2 positive tumors should be considered positive, as in human breast cancer. The lack of any known response to adjuvant endocrine therapy of ER- and PR-positive CMTs prevents the use of the biological positive/negative threshold applied in human breast cancer. IHC results of ER and PR in CMTs should be reported as a sum of the percentage of positive cells and the intensity of immunolabeling (Allred score). Incorporation of these recommendations in future studies, either prospective or retrospective, will provide a mechanism for the direct comparison of studies and will help to determine whether these biomarkers have prognostic significance. Finally, these biomarkers may ascertain the most appropriate treatment(s) for canine malignant mammary neoplasms.