Canine Mammary Tumors: A Review and Consensus of Standard Guidelines on Epithelial and Myoepithelial Phenotype Markers, HER2, and Hormone Receptor Assessment Using Immunohistochemistry
by L. Pena, A. Gama, M. H. Goldschmidt, J. Abadie, C. Benazzi, M. Castagnaro, L. Dıez, F. Gartner, E. Hellmen, M. Kiupel, Y. Millan, M. A. Miller, F. Nguyen, A. Poli, G. Sarli, V. Zappulli, and J. Martın de las Mulas
Veterinary Pathology, 2014, 51(1): 127-145
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 3þ 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.
by L. Pena, A. Gama, M. H. Goldschmidt, J. Abadie, C. Benazzi, M. Castagnaro, L. Dıez, F. Gartner, E. Hellmen, M. Kiupel, Y. Millan, M. A. Miller, F. Nguyen, A. Poli, G. Sarli, V. Zappulli, and J. Martın de las Mulas
Veterinary Pathology, 2014, 51(1): 127-145
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 3þ 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.