The estrogen effect; clinical and histopathological evidence of dichotomous influences in dogs with spontaneous mammary carcinomas


Autoři: Karin U. Sorenmo aff001;  Amy C. Durham aff002;  Enrico Radaelli aff003;  Veronica Kristiansen aff004;  Laura Peña aff005;  Michael H. Goldschmidt aff003;  Darko Stefanovski aff006
Působiště autorů: Department of Biomedical Sciences, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America aff001;  Penn Vet Cancer Center, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America aff002;  Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America aff003;  Department of Companion Animal Clinical Sciences, Veterinary Medicine and Biosciences, Norwegian University of Life Sciences, Oslo, Norway aff004;  Department of Animal Medicine, Surgery and Pathology, Veterinary School, Complutense University of Madrid, Madrid, Spain aff005;  Department of Clinical Studies, School of Veterinary Medicine, University of Pennsylvania - New Bolton Center, Kennett Square, Pennsylvania, United States of America aff006
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0224504

Souhrn

The purpose of this study was to investigate the associations and explore the relationships between hormonal factors (serum estrogen, estrogen receptors and ovariohysterectomy) and other clinical/histological prognostic factors and their impact on outcome in dogs with mammary carcinomas. Data from two separate prospective studies on dogs with spontaneous mammary carcinomas were used for this research. All dogs underwent standardized diagnostic testing, staging, surgery and follow-up examinations. Serum estrogen was analyzed by competitive enzyme immunoassay or radioimmunoassay, and tumor estrogen receptor (ER) expression was analyzed by immunohistochemistry. A total of 159 dogs were included; 130 were spayed and 29 remained. High serum estrogen was associated with an overall longer time to metastasis (p = 0.021). When stratifying based on spay group, the effect was only significant in spayed dogs, (p = 0.019). Positive tumor ER expression was also associated with a longer time to metastasis (p = 0.025), but similar to above, only in dogs that were spayed (p = 0.049). Further subgroup analysis revealed that high serum estrogen was significantly associated with improved survival in dogs with ER positive tumors, but only in spayed dogs (p = 0.0052). Interestingly, the effect of spaying was the opposite in dogs with ER negative tumors; here, intact dogs with high serum estrogen but ER negative tumors had a significantly longer time to metastasis (p = 0.036). Low serum estrogen was associated with increased risk for the development of non-mammary tumors in the post-operative period (p = 0.012). These results highlight the dual effect of estrogen in cancer: Estrogen acts as a pro-carcinogen in ER positive mammary tumors, but a may have a protective effect in ER negative tumors, potentially via non-receptor mechanisms. The latter is supported by the decreased risk for non-mammary tumors in dogs with high serum estrogen, and explains the increased incidence of certain non-mammary tumors in in dogs spayed at an early age.

Klíčová slova:

Breast cancer – Carcinomas – Dogs – Estrogens – Immunohistochemistry techniques – Metastasis – Surgical oncology – Veterinary diagnostics


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