The expression of the hormone receptors in the endometrium and endometrial polyps in postmenopausal women and its relationship to body mass index

OBJECTIVE: To evaluate and compare the relationship of body mass index (BMI) and the immunoexpression of estrogen (ER) and progesterone receptors (PR) in endometrial polyps (EP) and endometrium, in gland and stromal cells of postmenopausal women. METHODS: Thirty-five postmenopausal women with benign endometrial polyps, who had not been taking medication with hormonal effects for at least 6 months, were submitted to operative hysteroscopy. The presence of ER and PR were evaluated by immunohistochemical method using a semiquantitative analysis. RESULTS: BMI was significantly higher among patients with lower expression of ER in the glands of endometrium (p=0.02). EP and adjacent endometrium showed significantly higher proportion of positive cells in the glands than in the stroma, for both ER (p=0.0015 and 0.0018, respectively) and PR (p=0.0176 and p<0.0001, respectively). Glands and stroma cells showed significantly higher proportion of positive cells in polyps than in the endometrium, for ER (p<0.0001 and p=0.0034, respectively). CONCLUSIONS: The higher proportion of positive gland cells for ER in EP as compared to endometrium supports an implication of these receptors in the pathogenesis of polyps. Association of higher BMI with lower expression of ER in endometrial glands, but not in EP, may indicate that factors influencing ER expression do not affect EP, supporting an autonomous function of polyps.     

Expression of estrogen and progesterone receptors in the endometrium of fertile and infertile women

The aim of the research is investigation of the endometrial hormonal status during menstrual cycle infertile and infertile women. 68 endometrial biopsies from 18-45 years old women have been studied. Some changes of ER and PR expression during menstrual cycle both in fertile and infertile women has been founded. However the ER expression in endometrial stroma and PR in the glands in a proliferative stage of cycle of fertile women are higher than in a secretory stage. In infertile women the PR expression in endometrial glands is opposite.     

The early response of the postmenopausal endometrium to tamoxifen: expression of estrogen receptors,progesterone receptors,and Ki-67 antigen

OBJECTIVE: To enlighten the early response of endometrium to tamoxifen by assessing the expression of estrogen receptors, progesterone receptors, Ki-67, and the histological response in endometria from normal postmenopausal women treated for 21 days with tamoxifen. DESIGN: A total of 40 women, scheduled to undergo vaginal hysterectomy because of uterine prolapse, were randomly assigned to the tamoxifen group (20 mg/day; 20 women) or the control group (20 women). Samples were obtained from the upper and the lower thirds of the uterine cavity. Standard immunohistochemical staining of estrogen and progesterone receptors and of Ki-67 was performed on frozen sections. Staining was assessed using semiquantitative immunoreactivity scores. RESULTS: Simple endometrial hyperplasia was diagnosed in 18 of the 20 samples exposed to tamoxifen compared with only 2 of the 20 controls ( P< 0.0005). Staining was increased in both the epithelium and stroma in the tamoxifen samples, a difference that was significant for estrogen receptors in glandular epithelium (180 +/- 80 v 110 +/- 110; P< 0.05). Also, Ki-67 antigen was expressed more frequently in both glandular epithelium ( P< 0.05) and stroma ( P< 0.05) in the tamoxifen samples. CONCLUSIONS: Tamoxifen rapidly up-regulated the cell proliferation markers, an effect that was associated with enhanced growth as confirmed by increased expression of estrogen receptors and Ki-67, in addition to a high incidence of glandular hyperplasia.     

Detection of testosterone and estrogen receptors in the postmenopausal endometrium

OBJECTIVE: To detect the presence of testosterone and estrogen receptors in the stroma and glandular epithelium in the malignant and non-malignant endometrium. METHODS: One hundred and forty-five consecutively-enrolled peri- or postmenopausal patients were submitted to diagnostic or operative hysteroscopy. These patients either had a history of abnormal uterine bleeding or they were asymptomatic with an endometrial echo greater than 4 mm. The presence of estrogen and testosterone receptors was determined in endometrial samples by immunohistochemistry, using monoclonal antibodies and a streptavidin-biotin peroxidase complex system with diamino benzidine as the chromogen. RESULTS: Testosterone receptors were detected mainly in the stroma in the non-malignant endometrial lesions and in the atypical glandular epithelium in cases of estrogen-positive endometrial carcinomas. CONCLUSIONS: The presence of testosterone receptors in estrogen receptor positive endometrial carcinomas may be involved in the mechanism of cell proliferation in these tumors. The strong staining reaction for testosterone receptors in the endometrial glands can be considered one of the features of invasive malignancy.     

Immunohistochemical detection of estrogen and progesterone receptors in primary breast cancer

To evaluate the reliability of the immunohistochemical assay for estrogen receptor (ER) and progesterone receptor (PR) in the prognosis of patients with breast cancer, 83 primary tumors from the patients were studied. Immunohistochemical analysis was performed using antibody ER 1D5 for ER determination and antibody PR-ICA for PR determination. Of all tumors, ER and PR positivities were detected in 36.1% and 45.8% respectively. There was no significant relationship between ER, PR and age of the patients, tumor size or number of involved nodes. However, we found that only the immunohistochemical ER was a predictor of early recurrence in patients with primary breast cancer. In addition, there was no additive effect in recurrence-free survival when both receptor expressions were combined.     

Immunohistochemical analysis of estrogen receptor alpha, estrogen receptor beta and progesterone receptor in normal human endometrium

The endometrium expresses estrogen (ER) and progesterone receptors (PR), which are involved in autocrine and paracrine regulation processes in response to estrogen and progesterone. The aim of the present study was to evaluate immunohistochemical distribution patterns of estrogen receptor alpha (ER alpha), estrogen receptor beta (ER beta) and PR in normal human endometrial tissue with the use of monoclonal antibodies. Human endometria were obtained from 17 premenopausal patients undergoing surgery for non-malignant diseases and were classified to be in proliferative, early secretory and late secretory phases by histological and anamnestical means. Distribution patterns of the steroid receptors were evaluated using the IRS-score and the Mann-Whitney rank-sum test was used to compare the means. Correlation was assessed with the Spearman factor and linear regression analysis. ER alpha and PR expression decreased significantly (p<0.05) in glandular epithelium from the proliferative to the late secretory phase. ER beta expression showed a similar significant decrease (p<0.05), although staining intensity was lower than that of ER alpha. A significant correlation between expression of all three steroid receptors was observed (p<0.001). Distribution patterns of ER alpha, ER beta and PR in normal human endometrium showed a cyclic variation during the menstrual cycle. A significant correlation between expression of ER alpha, ER beta and PR was also demonstrated using regression analysis, indicating dependence of expression of these three steroid receptors. The present study shows the presence of steroid receptors in human endometrial epithelium, indicating that these cells respond to estrogen and progesterone and thus playing a significant role in endometrial physiology.     

Immunohistochemical expression of estrogen receptors in chondrosarcomas and enchondromas

Immunohistochemical expression of estrogen receptors alpha and beta was studied in chondrosarcomas and enchondromas and was correlated with chondrosarcoma grade, type, and dedifferentiation. Estrogen receptor alpha was studied in 37 chondrosarcomas, 10 enchondromas, and 2 extraskeletal myxoid chondrosarcomas. Estrogen receptor beta was studied in 23 chondrosarcomas, 6 enchondromas, and 2 extraskeletal myxoid chondrosarcomas. Ventana prediluted monoclonal anti-ER alpha (clone 6F11) and Biogenex prediluted polyclonal anti-ER beta were used on the Ventana ES autostainer and BenchMark XT IHC/ISH, respectively. Percent of cell staining and intensity (+, ++, or +++) was evaluated. Overall, 61% of conventional chondrosarcoma and 60% of enchondroma were positive for estrogen receptor alpha. Low-grade chondrosarcoma expressed estrogen receptor alpha more frequently than high-grade chondrosarcoma (P相似文献   

Endometriosis: Immunohistochemical analysis of oestrogen and progesterone receptors in endometriotic tissue and endometrium

The objective of the study was to compare the localization andstaining intensity of oestrogen and progesterone receptors inendometrium and endometriotic tissue. Using monoclonal antibodiestowards oestrogen and progesterone receptors, analysis was performedin 63 endometriotic samples from 40 women and compared to endometriumobtained simultaneously from 25 of the women. Using a stainingindex, ‘total immuno-staining score’, calculatedfrom the staining intensity multiplied by the fraction of positivecells, the receptor content was estimated semiquantitatively.The scores for both oestrogen and progesterone receptors werelower in endometriotic epithelial cells than in endometrialepithelial cells, but the differences reached statistical significanceonly for the progesterone receptor. No difference was foundfor stromal cells. There was a significant correlation betweenoestrogen receptor score in endometriotic tissue and in endometrium,but not for progesterone receptor score. In endometrium andvaginal and peritoneal endometriosis, the progesterone receptorscore showed similar values, higher than those in ovarian endometriosis.The data from this large immuno-histochemical study supportprevious results of quantitative steroid receptor analyses,indicating that the regulation of steroid effects, especiallythose of progesterone, differs between endometriotic and endometrialtissue.     

Effects of testosterone and estrogen treatment on the distribution of sex hormone receptors in the endometrium of postmenopausal women

OBJECTIVE: Our aim was to investigate the effects of the addition of testosterone to estrogen compared with those of estrogen alone on the expression and distribution of sex hormone receptors in glands and stroma of the endometrium of postmenopausal women. DESIGN: An open, randomized clinical study with parallel group comparison was performed in the Women's Health Research Unit at a university hospital. Thirty-one postmenopausal women were given oral estradiol valerate (2 mg daily) or estradiol valerate in combination with testosterone undecanoate (40 mg every 2 days) for 3 months. Before and at the end of treatment, endometrial biopsy samples were obtained, and expressions of estrogen receptor (ER)-alpha, ER-beta, progesterone receptor isoforms A and B, and androgen receptor (AR) were evaluated by immunohistochemical analysis. RESULTS: At baseline, expressions of ER-alpha and progesterone receptors were stronger in glands than in stroma, whereas the immunostaining of AR was stronger in stroma than in glands. After treatment, expressions of ER-alpha and progesterone receptors were up-regulated in both glands and stroma by both treatments, but to a lesser extent in glands by combined treatment. The expression of ER-beta in glands was significantly higher with combined treatment than with estrogen alone. Moreover, AR immunostaining was significantly higher after combined treatment than after treatment with estrogen alone. CONCLUSIONS: Expressions of AR and ER-beta were stronger in glands of the endometrium of postmenopausal women after treatment with testosterone added to estrogen than after estrogen alone. In contrast, expressions of ER-alpha and progesterone receptors were up-regulated in the endometrium with estrogen-alone treatment, whereas these expressions were less increased in glands after combined treatment. These data indicate that testosterone is involved in the regulation of sex hormone receptor expression in the postmenopausal endometrium and may therefore influence endometrial proliferation and differentiation.     

Correlation of estrogen and progesterone receptors with histologic differentiation in endometrial adenocarcinoma.

Endometrial carcinomas from 58 patients were graded histologically, and the histologic grade was compared with the estrogen and progesterone receptor content of the tumor tissues. Receptor content was determined by multiple concentration saturation analysis and sucrose density gradient analysis. A positive correlation was found between the presence of estrogen and progesterone receptors and the degree of tumor differentiation. The majority (85%) of well-differentiated lesions contained significant amounts of both steroid receptor proteins. In contrast, only 13% of the poorly differentiated lesions were characterized by the presence of detectable levels of both estrogen and progesterone receptor proteins. The relationship of receptor content and degree of differentiation to prognosis and potential for response to hormonal therapy is discussed.     

Immunohistochemical evaluation of human epidermal growth factor receptor 2 and estrogen and progesterone receptors in invasive breast cancer in women

Introduction

Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) expression are crucial in the biology of breast carcinoma. HER-2/neu gene is amplified and overexpressed in 15-30% of invasive breast cancers. HER-2-positive breast cancers have worse prognosis than HER-2 negative tumors and possess distinctive clinical features. The aim of this study was to assess the expression of HER2 in cancer tissue of patients with invasive breast cancer in correlation with tumor type, histological grade, tumor size, lymph node status, and expression of estrogen receptor and progesterone receptor.

Material and methods

Formalin-fixed, paraffin-embedded tissues from 40 patients with invasive HER-2-positive breast cancer and from 191 patients with HER-2-negative breast cancer were used in this study. HER2 expression was determined using the test HerceptTest™ DAKO.

Results

Among 231 cases of breast cancer, 18 invasive lobular carcinomas and 213 invasive ductal carcinomas were diagnosed. Sixty percent of HER-2-positive breast cancers were ER-positive compared with 77% in the HER-2-negative group (p = 0.002). The expression of PR was observed in 43% of HER-2-positive breast cancers and in 72% of HER2-negative tumors (p = 0.003). Excessive expression of HER2 protein was detected in 60% of patients positive for estrogen receptors, which may worsen prognosis in these patients.

Conclusions

Determination of HER2 overexpression in breast cancer patients, allows for a determination of a group of patients with a worse prognosis.     

Immunohistochemical expression of estrogen receptors alpha and beta in lobular neoplasia

The designation lobular neoplasia (LN) of the breast includes atypical lobular hyperplasia and lobular carcinoma in situ. Estrogen receptors (ER) play a significant role in breast carcinogenesis. In the present study, ER-alpha and ER-beta status are evaluated in 30 breast tissue specimens from patients whose main lesion was LN. A standard immunohistochemical procedure, using monoclonal antibodies for ER-alpha and ER-beta, was applied to the lesion and the adjacent normal breast tissues, the latter serving as control. In all cases, both receptors were expressed in LN as well as in normal breast ducts and lobules. Concerning ER-alpha, the Allred score and the percentage of ER-alpha-positive cells were significantly higher in LN than in the adjacent normal breast tissue. On the contrary, regarding ER-beta, the Allred score and the percentage of ER-beta-positive cells were significantly lower in LN compared with normal adjacent breast tissue. Greater increase in the percentage of ER-alpha-positive cells was associated with a smaller reduction in the percentage of ER-beta-positive cells and vice versa (Spearman’s rho = −0.5044, p = 0.001). In conclusion, upregulation of ER-alpha and downregulation of ER-beta may represent two discrete molecular events in LN pathogenesis. Of notice, a mutually limiting interaction may exist between the two events.     

雌、孕激素及其受体在子宫内膜癌中作用机制

雌、孕激素及其受体在子宫内膜癌的发生发展以及治疗中起重要作用,然而雌、孕激素及其受体在内膜癌中的具体作用机制仍未被充分阐释,全文综述了雌、孕激素及其受体的结构与生物学功能及其在子宫内膜癌中的参与机制,旨在为子宫内膜癌的临床诊疗提供新思路.     

Obesity affects expression of progesterone receptors and node metastasis of mammary carcinomas in postmenopausal women without a family history

Possible relationships between risk factors, such as obesity and a family history of breast cancer, and prognostic factors of mammary carcinomas were investigated by examining the body mass index of patients and the expression of estrogen (ER) and progesterone receptors (PgR), c-erbB-2 and p53, grade of histology, size of tumors and nodal status of mammary carcinomas. There was no significant difference in the body mass index of premenopausal patients either with or without a family history. For postmenopausal patients, the body mass index was significantly low in patients with a family history compared with patients without a family history. In premenopausal patients with or without a family history and in postmenopausal patients with a family history, there was no significant difference in the body mass index regardless of the mammary carcinoma prognostic factor, such as expression of ER, PgR, c-erbB-2 and p53, grade of histology, size of tumors and nodal status. However, in postmenopausal patients without a family history, body mass index was significantly high for patients with mammary carcinomas that had PgR expression and node metastasis. These results suggest that obesity may affect the PgR status and nodal status of mammary carcinomas in postmenopausal patients without a family history.     

An immunohistochemical comparison of endometrial polyps from postmenopausal women exposed and not exposed to HRT

OBJECTIVE: Our study set out to test the null hypothesis that oestrogen containing continuous combined hormone replacement therapy (HRT) would not affect the hormone receptor expression (oestrogen and progesterone receptors-ER, PR) or markers of cell proliferation/apoptosis (Ki67 and Bcl-2) in endometrial polyps from postmenopausal women exposed and not exposed to HRT. DESIGN: Immunohistochemical staining for ER, PR, Ki67 and Bcl-2 was performed on polyps obtained from two groups of postmenopausal women. SETTING: Polyps were obtained from postmenopausal women attending an outpatient hysteroscopy clinic in a district general hospital (Bradford Royal Infirmary, UK). POPULATION: Twenty-five postmenopausal women presenting with abnormal bleeding subsequently diagnosed with endometrial polyps (16 from women not exposed to HRT, 9 from women exposed to HRT). METHODS: Semiquantitative immunohistochemistry was performed. MAIN OUTCOME MEASURES: Significant differences or correlations in either hormone receptor expression or markers of cell proliferation/apoptosis between the two groups of polyps. RESULTS: There were no significant differences for hormone receptor expression (ER and PR) between endometrial polyps exposed and not exposed to HRT. Bcl-2 expression was higher than Ki67 in both groups, but polyps from HRT users had increased levels reflecting decreased apoptosis in these polyps. CONCLUSIONS: HRT has no demonstrable effect on polyp ER and PR expression. However, HRT does appear to inhibit apoptosis and cell proliferation in endometrial polyps, which may affect polyp growth.