Immunohistochemical Detection of Estrogen Receptors in Canine Mammary Tumors

Open access


Mammary tumors are among the most common neoplasms in intact female dogs. They have a complex morphology, usually affecting middle age and older bitches. Almost 50% of the mammary tumors in dogs are malignant neoplasms. Prognosis is based on several factors: stage, age, tumor size, metastasis, histopathology, ovariectomy status and hormone-receptor activity. Immunohistochemical (IHC) measurement has become increasingly an important diagnostic and prognostic parameter, with the development of monoclonal antibodies against nuclear estrogen and progestin receptors. The aim of this study was to detect the presence of ER receptors in malignant canine mammary tumors and to identify their association with the clinical course of the tumor. Mammary tumor samples have been obtained by mastectomy from dogs presented at our clinic. Detailed clinical examination, CBC and basic serum biochemical profile were performed in all patients. Surgery was the only treatment. Histopathological examination and immunohistochemical detection of estrogen α receptors (ERα) was performed on 8 formalin-fixed, paraffin-embedded tissue samples, using the PT LINK immunoperoxidase technique. Histopathological examination of the mammary tumor samples (n=11) revealed tubular adenocarcinoma (n=6,54.5%) and ductal adenocarcinoma (n=3, 27.3%), one patient with benign adenoma and one with mastitis. Patients with positive ER tumors are alive, without remission, while 3 of the patients that were ER negative died due to lung metastases. According to our results, it can be concluded that the appearance and development of canine mammary tumors is highly connected with ovarian steroid hormones and that immunostaining of the tumors may be used as a good prognostic parameter in these patients.

1. Moulton, J.E. (1990). Tumors of the mammary gland. In: Moulton J.E. (Ed.), Tumours in domestic animals (pp. 518–552). Berkeley: University of California Press.

2. Sorenmo, K. (2003). Canine mammary gland tumors. Vet Clin North Am Small Anim Pract. 33, 573–596.

3. Hellmen, E. (2005). Complex mammary tumours in the female dog: a review. Journal of Dairy Research 72, 90–97. PMid:16180726

4. Sorenmo, K.U., Kristiansen, V.M., Cofone, M.A., Shofer, F.S., Breen, A.M., Langeland, M., Mongil, C.M., Grondahl, A.M., Teige, J., Goldschmidt, M.H. (2009). Canine mammary gland tumours: a histological continuum from benign to malignant, clinical and histopathological evidence. Vet Comp Oncol. 7, 162–172. PMid:19691645

5. Misdorp, W. (2002). Tumors of the mammary gland. In: Meuten D.J. (Ed.), Tumors in domestic animals (pp. 575–606). Ames: Iowa State Press.

6. MacEwen, E.G., Withrow, S. (1996). Tumors of the mammary gland. Small Animal Oncology (pp. 356–372). Philadelphia: Saunders Company.

7. De Las Mulas, J. M., Millán, Y., Dios, R. (2005). A prospective analysis of immunohistochemically determined estrogen receptor α and progesterone receptor expression and host and tumor factors as predictors of disease-free period in mammary tumors of the dog. Veterinary Pathology Online 42 (2): 200-212. PMid:15753474

8. Nieto, A., Pena, L., Pérez-Alenza, M. D., Sanchez, M. A., Flores, J.M., Castano, M. (2000). Immunohistologic detection of estrogen receptor alpha in canine mammary tumors: clinical and pathologic associations and prognostic significance. Vet Pathol. 37 (3): 239–247. PMid:10810988

9. Lana, S.E., Rutteman, G.R., Withrow, S.J. (2007). Tumors of the mammary gland. In: Withrow S.J & MacEwen B.R. (Ed.), Small animal clinical oncology (pp. 455-477). Philadelphia: Saunders Company.

10. Murphy, S. (2008). Mammary tumours in dogs and cats. Inpractice 6, 334–339.

11. Beauvais, W., Cardwell, J. M., Brodbelt, D. C. (2012). The effect of neutering on the risk of mammary tumours in dogs – a systematic review. J Small Anim Pract. 53, 314–322. PMid:22647210

12. Las Mulas, J.M., Millan, Y., Dios R. (2005). A prospective analysis of immunohistochemically determined estrogen receptor alpha and progesterone receptor expression and host and tumor factors as predictors of disease-free period in mammary tumors of the dog. Vet Pathol. 42, 200-212. PMid:15753474

13. Cork, D. M. W., Lennard, T. W. J., Tyson-Capper, A. J. (2008). Alternative splicing and the progesterone receptor in breast cancer. Breast Cancer Res. 10 (3): 207. PMid:18557990 PMCid:PMC2481493

14. Misdorp, W., Hellmen, E., Else, R.W. (1999). Mammary tumours and dysplasia in dogs and cats. Histologic classification of tumours of domestic animals. Second series (pp. 3-6). Washington DC: Armed Forces Institute of Pathology.

15. Sorenmo, K.U., Shoferm, F.S., Goldschmidt, M.H. (2000). Effect of spaying and timing of spaying on survival of dogs with mammary carcinoma. J Vet Intern Med. 14, 266–270. PMid:10830539

16. Thuroczy, J., Reisvaag, G. J. K., Perge, E., Tibold, A., Szilagyi, J., Balogh, L. (2007). Immunohistochemical detection of progesterone and cellular proliferation in canine mammary tumours. J Comp Pathol. 137 (2-3): 122–129. PMid:17645888

17. Diaz, L. K., Sneige, N. (2005). Estrogen receptor analysis for breast cancer: current issues and keys to increasing testing accuracy. Adv Anat Pathol. 12 (1): 10–19. PMid:15614160

18. Port Louis, L.R., Varshney, K.C., Nair, M.G. (2012). An immunohistochemical study on the expression of sex steroid receptors in canine mammary tumors. ISRN VetSci. 1-7. PMid:23738123 PMCid:PMC3658582

19. Rutteman, G.R., Misdorpl, W., Blankenstein, M.A., Van den Brom, W.E. (1988). Oestrogen (ER) and progestin receptors (PR) in mammary tissue of the female dog: Different receptor profile in non-malignant and malignant states. Br J Cancer. 58, 594-599. PMid:3219269 PMCid:PMC2246835

20. Mariotti, F., Giacomo, R., Subeide, M. (2013). Immunohistochemical evaluation of ovarian hormonal receptors in canine mammary tumors. Open J Vet Med. 3, 104-110.

21. Spoerri, M., Guscetti, F., Hartnack, S., Boos, A., Oei, C., Balogh, O., Nowaczyk, R. M., Michel, E., Reichler, I. M., Kowalewski, M. P. (2015). Endocrine control of canine mammary neoplasms: serum reproductive hormone levels and tissue expression of steroid hormone, prolactin and growth hormone receptors. BMC Vet Res. 11, 235. PMid:26370564 PMCid:PMC4570623

22. Chen, Y.M., Lee, C.S., Wright, P.J. (2006). The roles of progestagen and uterine irritant in the maintenance of cystic endometrial hyperplasia in the canine uterus. Theriogenology 66, 1537–1544. PMid:16472854

23. Hagman, R. (2014). Diagnostic and prognostic markers for uterine diseases in dogs. Reprod Dom Anim. 49 (2): 16–20. PMid:24947856

24. Queiroga, F.L., Perez-Alenza, M.D., Silvan, G., Pena, L., Lopes, C., Illera, J.C. (2005). Role of steroid hormones and prolactin in canine mammary cancer. J Steroid Biochem Mol Biol. 94, 181–187. PMid:15862964

Macedonian Veterinary Review

The Journal of the Faculty of Veterinary Medicine-Skopje at the Ss. Cyril and Methodius University in Skopje

Journal Information

CiteScore 2017: 0.32

SCImago Journal Rank (SJR) 2017: 0.195
Source Normalized Impact per Paper (SNIP) 2017: 0.387


All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 112 110 9
PDF Downloads 46 46 6