Canine Mammary Tumors

Abstract

Although there have been several studies on the use of immunohistochemical biomarkers of canine mammary tumors (CMTs), the results are difficult to compare. This article provides guidelines on the most useful immunohistochemical markers to standardize their use and understand how outcomes are measured, thus ensuring reproducibility of results. We have reviewed the biomarkers of canine mammary epithelial and myoepithelial cells and identified those biomarkers that are most useful and those biomarkers for 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 (ERs), and progesterone receptors (PRs) 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 found 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 used in human breast cancer. Immunohistochemistry results of ER and PR in CMTs should be reported as the 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.

Expression of Podoplanin in Mammary Cancers in Female Dogs

“…Similar to us, the co-expression of PDPN in CAFs with HER2 receptor expression has also been demonstrated in cancer cells in IDC in women (15). HER2 is an important marker used in the diagnosis of breast cancer in women, while it is more and more frequently used for IHC tests in veterinary medicine (9)(10)(11). This receptor participates in the oncogenesis processes, by affecting cancer cell migration, increasing angiogenesis, and metastasis of cancer cells (9)(10)(11)44).…”

“…HER2 is an important marker used in the diagnosis of breast cancer in women, while it is more and more frequently used for IHC tests in veterinary medicine (9)(10)(11). This receptor participates in the oncogenesis processes, by affecting cancer cell migration, increasing angiogenesis, and metastasis of cancer cells (9)(10)(11)44). In these published studies, there is no relationship reported between the intensity of the HER2 receptor expression and the level of PDPN expression in CAFs in mammary tumours in bitches.…”

Establishment and Characterization of a New Cell Line of Canine Inflammatory Mammary Cancer: IPC-366

“…The primary canine mammary tumor, the cell line and xenotransplanted tumors were considered positive for AE1/AE3, CK-14, p63, vimentin, actin, E-Cad and COX-2 when more than 10% of the neoplastic cells were positive [ 21 ]. Beside this, IPC-366 phenotype markers were scored in pellet sections by a computer assisted image analyzer (image J), counting up to 1000 cells.…”

Estrogen receptor-α, progesterone receptor, and c-erbB/HER-family receptor mRNA detection and phenotype analysis in spontaneous canine models of breast cancer

“…Diagnosis and staging of these tumors is currently achieved by using a combination of pathology and physical diagnosis [15], although attempts have been made to apply immunohistochemical analysis to this problem, which can be challenging due to extended/variable fixation and sectioning artifacts and the requirement for specific target labeling [162225]. As a result, diagnosis and staging of canine mammary tumors is still largely based on standard traditional pathological analysis.…”