Oestrogen (ER) and progestin receptors (PR) in mammary tissue of the female dog: different receptor profile in non-malignant and malignant states

Abstract

Summary Oestrogen (ER) and progestin receptors (PR) were measured in cytosols from histologically normal mammary tissues (n=30), and in benign (n=59) and malignant mammary lesions (n=49) from female dogs. Receptor levels .5 fmol mg-1 protein were considered positive. The presence of histologically normal mammary epithelium within specimens of primary tumours was noticed as a factor that may cause falsepositive receptor results. Receptor levels in non-malignant tissues, and the receptor status of primary cancers did not vary significantly with regard to the phase of oestrous cycle (anoestrus/metoestrus) or the influence of exogenous progestins. ER-or PR-positivity was more frequent and levels of both receptors were higher in 'normal' tissues and in benign lesions than in primary cancers (P<0.001). ER and PR levels were higher in benign lesions of dogs also developing malignant mammary tumours than in benign lesions of dogs that did not (P<0.02 and P<0.05, respectively). Regional and distant cancer metastases were frequently receptornegative. In some dogs heterogeneity of receptor status was found between different sites of the same cancer.These findings indicate that in non-malignant mammary tissues of adult female dogs expression of the genes encoding ER and PR is common. In malignant tumours this property may become lost, in particular in advanced states of disease.Mammary cancer in the dog and in the human have several features in common, including the spontaneous occurrence and the sparing effect of ovariohysterectomy if performed early in life (Schneider et al., 1969, Feinleib, 1968. Oestrogen (ER) and progestin receptors (PR) have been found in a large proportion of mammary cancers in both species (Raynaud et al., 1981;McGuire et al., 1982;Pierrepoint et al., 1984), indicating a role for sex steroid hormones in growth of such tumours. The receptor status of human breast cancer has become established as a useful predictor of the likelihood of response of the disease to endocrine therapy (McGuire et al., 1982) and has also been found to be related to the degree of differentiation (Fisher et al., 1987). These observations may be interpreted as indications that steroid receptor presence in a tumour reflects persistence of normal cell characteristics. It has been difficult, however, to detect substantial amounts of ER in adult normal human breast tissue (Wagner & Jungblut, 1976). This has led to the reverse view, namely, that expression of hormone receptors reflects a feature related to the process of neoplastic transformation (Israel & Band, 1984).The present study was undertaken in order to determine the ER and PR profile of histologically non-affected mammary glands and of benign and malignant (primary and/or metastatic) proliferative lesions in the dog. Results were related to histopathological and some clinical features of affected dogs. Results of a limited number of these determinations have been included in other reports Rutteman et al., , 1988 Those that were not used for ER/PR analysis were always exam...

Köpek Meme Tümörlerinde Östrojen Reseptör, Progesteron Reseptör ve Ki-67 Antikor İşaretlenmelerinin İmmunopatolojik Olarak Araştırılması

“…This significant differences between benign and malign mammary tumours demonstrated that both hormone receptors and Ki-67 receptors had independent prognostic value. De Las Mulas et al [4] , Geraldes et al [28] , Rutteman et al [32] , Donnay et al [33] and Nieto et al [34] reported compatible results to present study.…”

“…Rutteman et al [32] reported that ER, PR scores and Ki-67 values of both benign and malignant mammary tumours showed a non-significant inverse correlation. ER and PR expression decreased significantly with increased values of Ki-67, they reported that these decreases in hormone receptors depend to the increased cellular transformation and the loss of stimulant effects of hormones on epithelial tumour cells.…”

Hyperoestrogenism and mammary adenosis associated with a metastatic Sertoli cell tumour in a male Pekingese dog

“…As in human breast cancer, there is increasing evidence that canine mammary tissue progresses from normal through dysplastic and benign stages before producing a malignant tumour (Sorenmo et al 2009); this is hormonally driven, but alterations in hormone receptors in more aggressive tumours suggest that as they progress the lesions change to become less reliant on external, hormonal stimuli (Geraldes et al 2000). This is further supported by lower oestrogen receptor levels in metastatic lesions (Rutteman et al 1988).…”

Canine Mammary Tumors: Risk Factors, Prognosis and Treatments

“…The presence of estrogen and progesterone receptors (ER and PR, respectively) in neoplastic mammary tissue has been demonstrated, and their expressions seem to be more frequent in BMT than in MMT (MacEwen et al, 1982;Inaba et al, 1984;Rutteman et al, 1988;Donnay et al, 1995, Martín de las Mulas et al, 2005Millanta et al, 2005). However, a recent study has found that more than half of both BMT and MMT were negative for ER and PR, indicating lack of correlation between tumor type and ER and PR expression (Toniti et al, 2009).…”