Hormonal Homologies between Canine Mammary Cancer and Human Breast Cancer in a Series of Cases

Abstract

The validity of spontaneous canine mammary cancer (CMC) as a natural model for the study of human breast cancer (HBC) from a hormonal point of view has never been thoroughly investigated. In this study, we analyzed the immunohistochemical expression of aromatase (Arom) and steroid receptors [estrogen receptor α (ER α), estrogen receptor β (ER β), progesterone receptor (PR) and androgen receptor (AR)] and intratumor steroid hormone levels of 17β-estradiol (E2), estrone sulfate (SO4E1), progesterone (P4), androstenedione (A4), dehydroepiandrosterone (DHEA), and testosterone (T) in 78 samples of mammary cancer-51 human breast cancer (HBC) and 27 canine mammary cancer (CMC)-and corresponding controls. Frequency of tumors expressing Arom, ERβ, PR, and AR was similar in both species, whereas ERα+ tumors were less frequent in the canine species. There was a closer similarity between premenopausal HBC and CMC. In HBC and CMC, all hormones assayed were increased in tumors compared to control samples. Intratumor androgen levels were similar in the two species, although levels of progesterone and estrogens were higher in the HBC samples than the CMC samples. Statistical associations among Arom, receptors, and hormones analyzed suggest that the major hormonal influence in both species is estrogenic through the ER, being the α isoform predominant in the human samples. Our findings further support CMC as a spontaneous model for the study of HBC, especially premenopausal HBC, although several differences, such as the more prevalent ERα immunoexpression and higher intratumor levels of estrogens and P4 in HBC, should be taken into account in comparative hormonal studies.

Keywords: aromatase; breast cancer; canine mammary cancer; hormones; steroid receptors.

Figure 1

(A,B) HBC. Invasive papillary carcinoma. Original magnification (OM) ×10: (A) positive Arom immunostaining; (B) positive ERα immunostaining. (C,D) CMC. Tubulopapillary carcinoma. OM ×10: (C) positive Arom immunostaining; (D) positive ERβ immunostaining. (E,F) HBC. Invasive ductal carcinoma. OM ×40: (E) negative Arom immunostaining; (F) positive AR immunostaining. (G,H) CMC. Tubular carcinoma. OM ×10: (G) positive Arom immunostaining; (H) positive PR immunostaining.