Comparison of estrogen and progesterone receptor expression in normal and tumor mammary tissues from dogs

Abstract

SUMMARY Concentrations of estrogen (er) and progesterone (pr) receptors were measured by radioreceptor assay in tumor (n = 319) and normal (n = 166) mammary tissue from 248 bitches. Correlations between er and pr and between receptor expression in tumor and normal mammary tissue from the same bitches were evaluated. The influence of tumor, clinical, or hormonal variables on receptor expression also was studied. Approximately 80% of tumor and 95% of normal mammary tissue expressed detectable concentrations of er, pr, or both. Direct correlation was found between er and pr concentrations in normal and tumor tissues. Median er concentrations were significantly higher (46 ± 47 fmol/mg of cytosolic protein vs 27 ± 24 fmol/mg of cytosolic protein; P = 0.0002) in normal than in tumor tissue. On the other hand, pr concentrations were significantly higher (57 ± 52 fmol/mg vs 77 ± 99 fmol/mg; P = 0.03) in tumors (especially benign tumors) than in normal tissue. Poorly differentiated malignant tumors expressed lower concentrations of receptors than did benign or well differentiated malignant tumors. The er and pr concentrations decreased with increasing size of the lesion. Hormonal status of the bitch significantly (P < 0.05) influenced receptor expression in normal tissue: bitches in the luteal phase of the estrous cycle had higher concentrations of er (69 ± 62 fmol/mg) than did ovariectomized bitches (24 ± 19 fmol/mg) or bitches in anestrus (38 ± 45 fmol/mg) or the follicular phase (13 ± 7 fmol/mg). For pr, higher concentrations were observed in normal tissue during anestrus than during pseudopregnancy or in bitches treated with medroxyprogesterone acetate. Similar, but nonsignificant, variations were seen in tumor tissue except in medroxyprogesterone acetate-treated bitches in which pr concentrations were high in tumors and low in normal tissue from the same bitches. Significant relation between age, hormonal history, number or location of lesions, and receptor expression was not observed. However, significantly (P < 0.05) lower receptor concentrations were found in the normal tissue from the 3 cranial pairs of mammary glands (er, 37 ± 45; pr, 43 ± 30 fmol/mg) than from the 2 caudal pairs (er, 51 ± 50; pr, 62 ± 53 fmol/mg). A direct correlation was found for both receptor concentrations between normal tissue adjacent to and distant from the lesions and between normal tissue adjacent to the lesion and the corresponding tumor. In comparison with that in normal tissue, the general mechanism of modulation of receptor expression seems not to be modified in benign lesions and well differentiated malignant tumors. However, hormonal sensitivity is lost in dedifferentiated tumors.