Immunohistologic Detection of Estrogen Receptor Alpha in Canine Mammary Tumors: Clinical and Pathologic Associations and Prognostic Significance

Abstract

Eighty-nine canine mammary tumors and dysplasias of 66 bitches were investigated to determine the immunohistochemical expression of classical estrogen receptor (ER-alpha) and its clinical and pathologic associations and prognostic value. A complete clinical examination was performed and reproductive history was evaluated. After surgery, all animals were followed-up for 18 months, with clinical examinations every 3-4 months. ER-alpha expression was higher in tumors of genitally intact and young bitches (P < 0.01, P < 0.01) and in animals with regular estrous periods (P = 0.03). Malignant tumors of the bitches with a previous clinical history of pseudopregnancy expressed significantly more ER-alpha (P = 0.04). Immunoexpression of ER-alpha decreased significantly with tumor size (P = 0.05) and skin ulceration (P = 0.01). Low levels of ER-alpha were significantly associated with lymph node involvement (P < 0.01). Malignant tumors had lower ER-alpha expression than did benign tumors (P < 0.01). Proliferation index measured by proliferating cell nuclear antigen immunostaining was inversely correlated with ER-alpha scores (P = 0.05) in all tumors. Low ER-alpha levels in primary malignant tumors were significantly associated with the occurrence of metastases in the follow-up (P = 0.03). Multivariate analyses were performed to determine the prognostic significance of some follow-up variables. ER-alpha value, Ki-67 index, and age were independent factors that could predict disease-free survival. Lymph node status, age, and ER-alpha index were independent prognostic factors for the overall survival. The immunohistochemical detection of ER-alpha in canine mammary tumors is a simple technique with prognostic value that could be useful in selecting appropriate hormonal therapy.

Quantitation of the Regional Lymph Node Metastatic Burden and Prognosis in Malignant Mammary Tumors of Dogs

“…In the present study, animals with metastasis had lower survival times than did animals without metastasis. These findings are similar to those reported in the literature 22, 23, 24, 25, 26…”

“…Corroborating previous findings,22, 23, 24, 25, 26 our study showed that the presence of lymph node metastasis is a negative prognostic factor. However, the analysis of these data with tumor size, histologic type, mitotic index, histologic grading, status of hormonal receptors, and cell proliferation markers may provide more consistent information in a multivariate analysis of the possible independent prognostic factors in dogs with malignant mammary tumors and may provide actual practical applications for the data presented in this study for clinical practice.…”

“…As in women, regional lymph node status has major impact on survival in dogs with mammary tumors 22, 23, 24, 25, 26, 27. In the present study, animals with metastasis had lower survival times than did animals without metastasis.…”

“…As in women, regional lymph node status has major impact on the survival of dogs with mammary tumors 22, 23, 24, 25, 26, 27. In dogs, the use of tracers for identifying SLNs is rarely used in routine practice, but recent studies have evaluated these techniques 28, 29…”

Common cancer in a wild animal: the California sea lion ( Zalophus californianus ) as an emerging model for carcinogenesis

“…Studies in other animals have identified similar associations. Increased ER-a and PR expression were found to be correlated with a better prognosis in canine mammary tumours [25,26]. In rabbits with uterine adenocarcinoma, however, expression of ER-a and PR did not reflect prognosis, despite varying hormone receptor expression playing a role in the development of two different types of tumours, papillary or tubular [27].…”