Studies on canine mammary tumours. II. Oestradiol and progesterone receptor binding capacity and histological type.

Tissue samples taken from the mammary gland of 42 dogs (age: 6 to 12 years) were examined. Thirty-eight samples showed neoplasia: 36 were epithelial while the remaining 2 proved to be connective tissue tumours. Thirty-four % of the neoplasms were new benign tumours (most frequently adenoma and fibroadenoma) and 66% were malignant ones (mainly adenocarcinoma). The oestrogen receptor (ER) and progesterone receptor (PR) binding capacity was determined on 21 tissue samples using the method of EORTC (1980). The connective tissue tumours and non-tumourous tissues contained no sexual steroid receptor. 71.4% of all tissue samples contained receptors. 61.9% of the samples was ER+, 42.8% was PR+, 33.3% contained both receptors, 28.6% was only ER+ and 9.5% only PR+. The average ER and PR binding capacity was 120.3 (5.0-622.8) and 266.7 (92.3-475.0) fmol/mg cytosol protein, respectively. No difference in receptor positivity was demonstrable between the benign and the malignant tumours. PR negativity accompanied by ER positivity was more common in the case of benign tumours. ER binding capacity tended to be correlated with age: this correlation could be described with a hyperboloid regression curve (r = -0.5931; 0.06 > p > 0.05).     

Cytoplasmic estrogen and progesterone receptors in canine endometrium during the estrous cycle

Estradiol and progesterone receptors (ER, PR) were characterized and measured in cytosols from canine endometrium, using saturation and sucrose-gradient centrifugation radioassays. Both receptors were demonstrated to be steroid- and tissue-specific saturable proteins, which bound the respective steroids with high affinity (dissociation constant [Kd] approximately 10(-9)M). Serum estradiol, progesterone, and endometrial cytosol receptor concentrations and receptor-binding affinity were measured for 25 bitches from which samples were obtained at 5 stages of the estrous cycle (5 bitches each): anestrus (A), the 3rd day of proestrus (P3), the 3rd day of estrus (E3), the 12th day after onset of estrus (E12), and the 28th day after onset of estrus (E28). Mean (+/- SEM) serum estradiol concentrations were 17.0 +/- 2.2 (A), 55.4 +/- 5.0 (P3), 89.4 +/- 24.9 (E3), 41.0 +/- 5.9 (E12), and 50.6 +/- 3.9 (E28) pg/ml. Mean (+/- SEM) serum progesterone concentrations were 0.4 +/- 0.1 (A), 1.5 +/- 0.2 (P3), 17.3 +/- 7.5 (E3), 41.6 +/- 9.5 (E12), and 25.8 +/- 3.2 (E28) ng/ml. Concentrations of ER increased significantly from 1.06 pmol/g of uterus during stage A to a peak concentration of 6.18 pmol/g of uterus at E12, followed by a gradual decrease to 0.69 pmol/g of uterus by E28. The PR concentrations increased from 3.01 pmol/g of uterus in stage A to 17.32 pmol/g of uterus at P3; PR concentrations, thereafter, decreased gradually to 1.85 pmol/g of uterus by E28. Dissociation constants were significantly higher at E12 for the ER (Kd = 2.6645 X 10(-9)M) and at P3 for the PR (Kd = 5.8282 X 10(-9)M) than at the other stages examined, indicating a decrease in receptor affinity during the periods of high receptor concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)     

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

The immunohistochemically determined estrogen receptor (ER) alpha (ERalpha) and progesterone receptor (PR) status, as well as recognized, well-accepted prognostic indicators and host factors were prospectively analyzed in 84 cases of primary canine mammary carcinoma for their effect on disease-free period (recurrence free, metastasis free, or combined) (DFP) after an observation period of 18 months. The presence of one or both receptors, as well as tumor size, lymph node status, histologic grading, intravascular growth, and necrosis, were of prognostic value for DFP. In multivariate analysis, only tumor size and histologic grading proved to be independent prognosticators. None of the host factors analyzed were of prognostic value for DFP. ERalpha, PR, or both were detected in 173 out of 228 tumors: 70 ERalpha and PR; 5 ERalpha only; 98 PR only. Statistically significant differences regarding the presence of one or both receptors were observed between benign and malignant tumors and between complex, mixed, and simple histologic subtypes of benign and malignant tumors. In the group of malignant tumors (n=155), the presence of one or both receptors was more frequent in tumors smaller than 3 cm, without lymph node metastasis, with tubulopapillary rather than solid patterns of growth among simple carcinomas, of histologic grades I and II, without both intravascular growth and necrosis, and with lymphocyte cell infiltrates. The most frequent groups of hormone receptors-positive tumors were the ERalpha-positive and PR-positive group among benign and the ERalpha-negative and PR-positive group among malignant tumors.     

Comparison of steroid receptor expression in normal, dysplastic, and neoplastic canine and feline mammary tissues

Steroid receptor expression was assessed by immunohistochemistry in neoplastic, hyperplastic/dysplastic, and normal mammary tissue samples removed from 68 queens and 47 bitches, using monoclonal antibodies against human oestrogen-alpha (ER) and progesterone receptors (PR). Mammary lesions were classified according to World Health Organization (WHO) criteria, and all animals with invasive carcinomas were clinically followed for 2 years. Stromal and/or lymphatic invasion and histological grading were also recorded. In both species, ER expression was significantly higher in healthy tissues, hyperplastic/dysplastic lesions, and benign tumours than in carcinomas. The loss of ER expression was more marked in feline than in canine carcinomas. In queens, PR expression increased in dysplastic lesions and "in situ" carcinomas and decreased in invasive carcinomas, even if parts of these tumours were still PR-positive. In bitches no significant variation in PR expression was observed between normal tissue, dysplasias, and benign neoplasms, but was significantly lower in carcinomas. In both species ER and PR expression in invasive carcinomas did not correlate either with histological parameters or overall survival time. This study demonstrates several differences in steroid hormone dependency between the two species. The percentage of PR-positive feline carcinomas suggests a possible role of progesterone in promoting early tumour cell growth in queens. The low percentage of ER-positive invasive carcinomas further demonstrated the aggressive phenotype and behaviour of feline mammary tumours.     

Androgen and estrogen receptors in bovine skeletal muscle: relation to steroid-induced allometric muscle growth

The presence of free androgen (AR) and estrogen receptors (ER) was demonstrated in bovine skeletal muscle. Androgen receptor concentrations in neck muscle from cattle of different sexes and stages of development were related to hormonal status. In mature bulls (mean weight 600 kg), no free AR was detectable. Highest AR concentrations were measured in mature bulls (517 kg) castrated 24 h prior to slaughter (.85 +/- .21 fmol/mg protein). In female calves (155 kg), AR concentrations (.56 +/- .14 fmol/mg) were greater (P less than .01) than in male calves (.20 +/- .08 fmol/mg) of the same weight. Androgen receptors and ER in skeletal muscle of neck, shoulder, abdomen and hind leg of female and male calves were compared. There was no significant difference between AR concentrations in the neck, shoulder and hind leg, but concentrations were lower (P less than .05) in abdominal muscle. Estrogen receptor concentrations in neck, shoulder, abdomen and hind leg were not different between sexes (P less than .05). In male calves, ER content was lower (P less than .05) in abdominal than in other muscles. Estrogen receptor concentrations in muscles of female calves did not differ (P less than .05). The pronounced sensitivity to estrogens and androgens in the neck, shoulder, and hind leg of calves, being free of the respective hormone, may partly explain the characteristic conformation in calves treated with estrogenic and androgenic steroids and the sexual dimorphism of muscle growth.     

Progesterone receptors in feline mammary adenocarcinomas

Estradiol and progesterone receptors were measured in tumor cytosols from 3 intact and 4 neutered female cats with spontaneously occurring mammary adenocarcinomas. Serum from 2 of the intact cats which had been in estrus 4 and 4 to 6 weeks before tumor excision contained progesterone concentrations of 16.2 and 2.2 ng/ml, respectively; serum progesterone in the other cats was less than 2 ng/ml. Estradiol receptors were not detected in any cytosols. Progesterone receptors were detected in all of the cytosols, in concentrations ranging from 4.0 to 11.7 (mean = 7.2) fmol/mg of protein. Scatchard plot analysis of tumor cytosol from an 8th cat with mammary adenocarcinoma revealed presence of high affinity progesterone binding with a dissociation constant (Kd) of 3.47 nM. Tumor receptor content could not be correlated with stage of the estrous cycle nor with whether the cat was intact or neutered.     

Changes in oestrogen,progesterone and epidermal growth factor receptor concentrations and affinities during the oestrous cycle in the normal mammary gland and uterus of dogs

Changes in the concentrations and affinities of receptors for oestrogen (ER), progesterone (PR) and epidermal growth factor (EGF-R) were studied in mammary glands of healthy bitches with regard to age, the location in the mammary chain and the stage of the oestrous cycle. Uterus was used as the reference tissue for the evaluation of steroid receptors. Mammary and uterine samples from 7 healthy bitches were taken at five stages of the oestrous cycle in such a way that all the locations in the mammary chain were represented at each stage of the cycle (10 samples/dog). ER, PR and EGF-R were detected by biochemical assays using increasing concentrations of tritiated (steroids) or iodinated (EGF) ligands. A significant direct correlation was found between the ER and PR concentrations for mammary and uterine samples. No significant correlation was found between the steroid receptors and EGF-R concentrations. Mammary ER concentrations were significantly higher in bitches of 5 years of age or older than in younger ones; in posterior glands (4th and 5th pairs) than in anterior glands; and in the mid-luteal phase. Mammary PR did not vary significantly with age or location but was significantly lower in the early luteal phase than in other phases. A similar decrease in PR concentrations was observed in the uterus during the early luteal phase and uterine ER and PR concentrations were very low in the mid-luteal phase. Mammary EGF-R were not significantly higher in the early or mid-luteal phase than in pro-oestrus or anoestrus.The differences observed between the uterine and mammary steroid receptor concentrations during the oestrous cycle could be due to different mechanisms for regulating steroid receptor expression in the two tissues. Mammary EGF-R concentrations may be linked, as in other species, to cellular proliferation and/or to the serum progesterone concentrations.Abbreviations BSA bovine serum albumin - EGF epidermal growth factor - EGF-R receptor for epidermal growth factor - ER oestrogen receptor - K _d dissociation constant - LH luteinizing hormone - p probability of error - PR progesterone receptor     

Progesterone receptors in normal,dysplastic and tumourous feline mammary glands. Comparison with oestrogen receptors status

The aims of the study were to standardise an immunohistochemical (IHC) method for the detection of progesterone receptors (PR) on formalin-fixed, paraffin wax-embedded tissue sections of feline mammary gland tumours and dysplasias, comparing the results with those obtained using the radiolabelled ligand dextran coated charcoal (DCC) assay applied to frozen tissue samples from the same cases. Also, to define the immunohistochemical distribution of PR in the different cellular compartments of the lesions and to compare the oestrogen receptor (ER) and PR status of the feline mammary lesions. Proliferative mammary lesions collected from 34 cats were studied; 25 malignant tumours and 9 benign tumours and dysplasias. PR protein was present at a concentration of 5 fmol mg(-1) (positivity threshold) in 37.5 per cent of malignant tumours and 66.7 per cent of benign tumours and dysplasias while immunoreative products to PR antibody were found in the nuclei of tumour cells in 38.5 per cent and 66.7 per cent of the cases, respectively. Concordance between DCC-PR and IHC-PR was 88.5 per cent (P<0.001). The specificity (true negatives) and sensitivity (true positives) of the IHC method were 89.4 per cent and 87.5 per cent respectively. The presence of PR was linked to the absence of ovariectomy (P<0.02). Oestrogen receptors, detected by either method, were also detected in half the cases in which PR had been detected. In malignant tumours, the most prevalent groups were the ER + PR + and ER-PR + groups.     

Coordinate expression of cytokeratins 7 and 20 in feline and canine carcinomas.

Forty-seven feline and 60 canine epithelial tumors were studied to test the coordinate expression of cytokeratin 7 (CK 7) and cytokeratin 20 (CK 20) using commercially available monoclonal antibodies and an avidin-biotin immunoperoxidase staining technique. Previously, the distribution of both cytokeratins was examined in normal tissues from 4 cats and 4 dogs. The pattern of distribution of CK 7 in normal tissues was similar, with minor differences, to that described in humans, whereas the reactivity pattern of CK 20 in cats and dogs was wider than that in humans. The subset of tumors strongly expressing CK 7 and CK 20 included pancreatic adenocarcinomas (100%), transitional cell carcinomas (75%), and endometrial carcinomas (67%) in the cat. None of the canine tumors had this immunophenotype. Feline (50%) and canine (56%) mammary gland carcinomas and canine cholangiocarcinomas (67%) were the only tumors presenting the CK 7 +/CK 20- immunophenotype, whereas the CK 7-/CK 20+ immunophenotype included thyroid carcinomas (100%), intestinal adenocarcinomas (60%), bronchioloalveolar carcinomas (50%), and renal carcinomas (50%) in the cat and intestinal adenocarcinomas (56%), gastric adenocarcinomas (50%), and ovarian carcinomas (50%) in the dog. The CK 7-/CK 20- immunophenotype included the rest of the analyzed tumors. The immunohistochemical evaluation of coordinate expression of both CK 7 and CK 20 in feline and canine carcinomas using monoclonal antibodies provides important information that can help to discriminate among carcinomas from different primary sites and could be particularly helpful in the determination of the primary site of origin of carcinomas presenting as metastatic disease.     

The immunohistochemical evaluation of estrogen receptor-alpha and progesterone receptors of normal, hyperplastic, and neoplastic endometrium in 88 pet rabbits

The expression of estrogen receptor-alpha (ER) and progesterone receptor (PR) in normal, hyperplastic, and neoplastic endometrium in rabbits was evaluated by immunohistochemistry. The tissues evaluated were 27 normal uteri, 19 cases with endometrial hyperplasia, and 42 adenocarcinomas. Sixteen of 27 cases of normal uteri (59.3%) and 13 out of 19 hyperplasias (68.4%) stained positive with both ER-alpha and PR. Adenocarcinomas were further subdivided into 26 papillary and 16 tubular/solid adenocarcinomas. Papillary adenocarcinoma infiltrated the myometrium late in the disease and caused attenuation of the myometrium. In contrast, tubular/solid adenocarcinoma invaded into the deep myometrium early in the disease without thinning of the myometrium. Twenty-one cases out of 26 (80.8%) cases of papillary adenocarcinoma were both ER-alpha and PR negative, whereas 15 out of 16 (93.8%) of the tubular/solid adenocarcinomas were positive for ER-alpha, PR, or both. The total immunoreactive scores of ER-alpha, PR, and mode of myometrial invasion were significantly different between histopathologic types. This suggests that there may be 2 different developmental pathways for uterine adenocarcinomas in the rabbit.     

Evaluation of canine mast cell tumors for presence of estrogen receptors

Ten tumors from 7 dogs were analyzed for estrogen receptors. Of 9 determined to be mast cell tumors, 6 were determined not to have estrogen receptors (less than 3 fmol of estradiol/mg of cytosol protein) and 3 were questionable (3 to 10 fmol of estradiol/mg). One tumor was a mixed mammary tumor and was determined to have estrogen receptors (12 fmol of estradiol/mg). Histologic grading of the mast cell tumors did not suggest a correlation with estrogen receptor values.     

The bovine placenta; a source and target of steroid hormones: observations during the second half of gestation

Apart from estrone-3-sulfate (E1S) the bovine placenta produces progesterone (P4), though the corpus luteum is the major source of P4 responsible for maintaining pregnancy. So far the biological function of placental steroids in cattle is largely unknown. However, since the local availability of free estrone (E1) in the placenta seems to be controlled by sulfatase and sulfotranferase, the hypothesis was developed that placental estrogens and P4 might act as local regulatory factors. To test for such a function placentomes from 150, 220, 240, 270 days (D) pregnant and parturient cows were screened immunohistochemically for progesterone and estrogen receptors (PR, ER). PR were found at all stages in the caruncle in stromal cells and capillary pericytes but only at parturition in arterial walls. Percentage of PR-positive caruncular stromal cells (CSC) increased (P<0.05) from 51.8+/-2.6% at D150 to 58.9+/-1.8% at parturition. ER were detected in CSC, caruncular epithelial (CE) cells and in caruncular capillary pericytes. Mean percentage of ER-positive CSC decreased from 39.0+/-5.9% in pregnant cows to 17.5+/-8.3% at parturition (P<0.05). In CE all cells exhibited positive signals with the exception of those immediately surrounding large primary chorionic villi. Proliferation was assessed immunohistochemically by determining the percentage of Ki67-antigen positive cells. Highest values (P<0.001) were obtained for CE (58.0-68.3%), followed by the trophoblast (23.3-25.4%), CSC (10.6-45.3%) and the stroma of the chorionic villi (2.9-10.5%). A transient depression of proliferation in CSC between D150-270 (P<0.05) paralleled local estrogen tissue concentrations. The results suggest that placental estrogens and P4 are important factors controlling caruncular growth, differentiation and function.     

Expression of oestrogen and progesterone receptors in canine sebaceous gland tumours

Sebaceous gland oestrogen α (ERα) and progesterone (PR) receptor expression was examined immunohistochemically in 26 and 32 dogs respectively with sebaceous gland hyperplasia/adenomas, epitheliomas and carcinomas, and in the glands of 10 healthy controls. The mean percentage of ERα positive nuclei in control sebaceous glands was 21.31% compared with 11.5% in hyperplasia/adenoma‐type lesions, although these values were not statistically different. In sebaceous gland epitheliomas and carcinomas, positive basal cells represented 7.86% and 3.53% of neoplastic cells respectively and these mean percentages were significantly lower in epitheliomas (P < 0.024) and carcinomas (P < 0.015) than in controls. The mean percentage of PR‐positive nuclei in control sebaceous glands was 23.96%, similar to the 22.07% found in hyperplasia/adenoma‐type lesions. In sebaceous gland epitheliomas and carcinomas, positive cells were scarce and represented 13.5% and 4.06% of neoplastic cells respectively. Differences in the percentage of positive cells between normal and pathological glands reached statistical significance for carcinomas (P < 0.043). In the control group there was greater PR (P < 0.001) and ERα expression (P < 0.014) in sebaceous glands in female dogs. The PR and ERα immunoreactivity in each category of neoplastic lesions could not be analysed because sample size was too small but when all the sebaceous gland tumours were grouped and analysed, no sex difference was found. The results suggest that oestrogen and progesterone receptor expression is reduced in some canine sebaceous gland tumours. These changes may represent a contributing factor for tumour growth or simply be a consequence of tumour progression.     

M41型IBV对输卵管中雌激素、孕激素受体及胰岛素生长因子-Ⅰ表达的影响

本试验通过相对定量RT-PCR检测接种M41型鸡传染性支气管炎病毒(infectious bronchitis virus,IBV)对蛋鸡输卵管各部分(蛋白部、峡部、伞部和子宫)雌激素受体(ER)、孕激素受体(PR)及胰岛素生长因子-Ⅰ(IGF-Ⅰ)mRNA表达的影响,研究IBV早期感染(10 d)抑制蛋鸡输卵管发育的作用机制。结果显示,输卵管各部均有ER、PR和IGF-Ⅰ mRNA的表达,染毒组ER、PR mRNA的表达量较正常对照组显著减少(P＜0.05),而IGF-Ⅰ的表达量较正常对照组显著增加(P＜0.05)。可见IBV可通过降低ER和 PR mRNA的表达水平,抑制输卵管对雌激素的应答能力而影响输卵管的发育;而IGF-Ⅰ可能是以自分泌、旁分泌方式在输卵管局部起作用,是输卵管生长的调节因子。     

Immunohistochemical characterization of estrogen and progesterone receptors in lymphoma of horses

Abstract: Immunohistochemical techniques were used to examine 29 cases of equine lymphoma for estrogen receptor (ER) and progesterone receptor (PR) expression. The lymphomas examined included T-cell-rich large B-cell lymphomas, B-cell neoplasms, and T-cell lymphomas. The individual cases were also classified according to the anatomic location of the tumors. One normal equine lymph node was also examined for ER and PR expression. All of the cases of equine lymphoma and the normal lymph node were negative for ER. A total of 16/29 (55%) PR-positive lymphomas were identified. Seven of the 12 (58%) T-cell-rich large B-cell lymphomas were positive, 7/11 (64%) B-cell tumors were positive, and 2/6 (33%) T-cell neoplasms were positive. Anatomically, 6/9 (66%) subcutaneous lymphomas were PR positive, 3/5 (60%) intrathoracic lymphomas were positive, 1/4 (25%) intra-abdominal lymphomas were positive, 2/5 (40%) intra-abdominal/intrathoracic lymphomas were positive, 1/2 (50%) upper airway lymphomas were positive, and 3/3 (100%) splenic lymphomas were positive. One case involving abdominal and thoracic tumors and leukemia was negative for PR expression. The normal lymph node contained a low percentage (1.9%) of PR-positive lymphocytes. The presence of PR in neoplastic equine lymphoid tissue indicates that these tumors may be responsive to serum progesterone. Also, identification of PR-positive cells in the normal lymph node suggests that PR may be constitu-tively expressed in normal equine lymphocytes. Further studies are needed to quantify PR levels in normal and malignant equine lymphoid tissue and to determine the usefulness of either progestin or antiprogestin drugs in the management of equine lymphoma.     

Sex differences in oestrogen receptor levels in adrenal glands of sheep during the breeding season

The concentrations of the oestrogen receptor (ER), and the mRNA levels of ER, progesterone receptor (PR) and insulin-like growth factor I (IGF-I) were characterised in adrenal glands and uterine tissue of adult Corriedale sheep during the breeding season. The sheep were of different sex and gonadal status. Ewes had higher levels of cytosolic ER in the adrenals than the rams (mean±S.E.M.: 7.3±2.0 fmol/mg protein and 2.5±1.0 fmol/mg protein, respectively; P=0.0091) and gonadectomy increased ER (mean±S.E.M.: 2.9±1.2 fmol/mg protein and 8.6±2.3 fmol/mg protein, intact and gonadectomised sheep, respectively; P=0.0071). No differences could be observed in mRNA levels for ER and IGF-I in the adrenal glands of all of the sheep. PR mRNA levels were reduced in ovariectomised ewes and enhanced in castrated rams (sex×gonadal status: P=0.009). PR mRNA levels tended to be higher in ewes in the follicular phase than in ovariectomised ewes and intact rams (P<0.1). All of the animals had positive nuclear staining for ER in the adrenal cortex, but no differences were observed between the groups. In this study, we demonstrated the existence of ER in the adrenal gland of sheep and found varying sensitivity to oestrogens as the ER levels differed among sex and gonadal status. These findings indicate that oestrogens most likely affect steroidogenesis directly at the adrenal cortex and suggest that oestrogens are partly responsible for the sex differences in cortisol secretion in sheep.     

Immunohistochemical analysis of estrogen receptors in feline mammary gland benign and malignant lesions: comparison with biochemical assay

Estrogen receptors (ER) were determined by both the biochemical dextran-coated charcoal (DCC-ER) and the immunohistochemical Avidin biotin-peroxidase complex (IHC-ER) methods in proliferative mammary lesions collected from 37 cats: 20 malignant tumors without metastasis at first presentation, seven malignant tumors with lung and/or lymph node metastases and 10 benign tumors and dysplasias. Total number of samples analyzed by both methods was 44. The DCC-ER method was applied to frozen tissue samples and the IHC-ER method was applied to neutral buffered formalin-fixed, paraffin wax-embedded tissue samples by using the NCL-6F11 monoclonal antibody. Biochemically, 21 (47.7%) cases had equal or more than 5 fmol/mg of protein (standard positivity threshold). Immunohistochemically, 11 (25%) cases were scored positive, the percentage of positive nuclei being statistically linked to the intensity of immunostaining. Normal mammary gland tissue (13 cases) and/or dysplastic areas (5 cases) found in the surroundings of the main lesion were IHC-ER positive in 76.9% and 40% of the cases, respectively. Concordance between DCC-ER and IHC-DCC was 72.7% and the results of the DCC and the IHC-ER methods were significantly correlated (P < 0.05) by the chi2 test. Specificity (true negatives) and sensitivity (true positives) of the ICH-ER method were 95.6% and 47.6%, respectively. One out of eleven DCC-ER positive and IHC-ER negative discordant cases (9.09%) was a DCC-ER false positive, because the surrounding normal mammary gland tissue was IHC-ER positive. The remaining 10 cases had ER content values equal or lower than 23 fmol/mg of protein, a figure that could represent the sensitivity threshold of the immunohistochemical method employed.     

Determination of estrogen receptors in canine mammary tumors

Dextran-coated charcoal assay with Scatchard plotting was used for the quantitative determination of high-affinity estradiol receptors (ER) in 10 canine mammary tumor cytosols. Mammary tumors diagnosed histopathologically as adenocarcinomas appeared to have a higher incidence of ER than those diagnosed as mixed mammary tumors. These receptors have a high affinity for estradiol with dissociation constants as determined by Scatchard analysis ranging from 1.2 to 2.0 X 10(-11) M. These dissociation constants are similar to those previously reported for the receptor-estradio interaction from target tissues in other species. The specific binding of the receptor for the hormone was diminished in the presence of an antiestrogenic compound. Our data suggest that canine mammary tumors with significant ER levels would respond favorably to antiestrogen therapy. With the demonstration of ER sites in canine mammary adenocarcinomas as presented herein, the potential for chemotherapeutic management appears to be encouraging.     

Classification and behavior of canine mammary epithelial neoplasms based on life-span observations in beagles.

As part of a study of the effects of low-level radiation, 1,343 Beagles, including 671 males and 672 females, were evaluated over their full lifetime for the occurrence of mammary neoplasia; there were 139 control males and 138 control females and 532 irradiated males and 534 irradiated females. All nodules found in surgical specimens or at necropsy were evaluated histologically. The overall incidence, metastasis and recurrence rates, and contribution to mortality of mammary neoplasms were determined. Based on this unique opportunity to correlate morphologic characteristics with ultimate biological behavior of all mammary tumors in a defined canine population, we propose a histogenetically based reclassification of epithelial mammary tumors. Of the 672 female dogs, 70.8% (476) had at least one mammary neoplasm; 60.7% (408) had more than one. Two male dogs had mammary neoplasms. Of 1,639 mammary carcinomas in the 672 females, 18.7% (307) were classified as ductular carcinomas (arising from the small interlobular or intralobular ductules), whereas 80.7% (1,322) were classified as adenocarcinomas of other histogenetic origin. Of 73 fatal carcinomas, ductular carcinomas accounted for 48 fatalities (65.8%), whereas other adenocarcinomas accounted for only 20 fatalities (27.4%). Radiation had no effect on this ratio. Ductular carcinomas also had a higher rate of metastasis than did adenocarcinomas. Existing classifications of mammary carcinomas do not recognize the characteristic morphologic features, the degree of malignancy, and the prognostic importance of these ductular carcinomas. Metastasis rates did not differ between simple and complex carcinomas or between those lesions and adenocarcinomas in mixed tumors. True carcinosarcomas metastasized more frequently (100%, or 5/5) than did adenocarcinomas in mixed tumors (34.4%, or 22/64), emphasizing the importance of not lumping these tumors under the classification of malignant mixed tumors.