Estrogen receptors,progesterone receptors,and cell proliferation in human breast cancer

Summary The breast is a target organ for estrogens and progesterone. These hormones control several functions of the normal and abnormal mammary epithelium including cell proliferation. Most of the actions of estrogens and progesterone are mediated via specific steroid receptors, and one would expect that proliferating cells should contain estrogen receptors (ER) and/or progesterone receptors (PR). However, the correlation between receptor expression and cell proliferation is still controversial. In the present study we have examined 29 human breast cancer samples; in 17 of them we evaluated the simultaneous ER and PR localization with that of proliferating cell nuclear antigen (PCNA) and silver-stained nucleolar organizer regions (AgNORs) in a cell-by-cell study. We found that in almost 50% of the tumor biopsies examined, the cells expressing ER were significantly associated with elevated cell proliferation. In another group (38%) there were not significant differences between ER expression and cell proliferation. In only one of the samples (6%) the cells expressing ER showed lower cell proliferation. The study also revealed that in 44% of the tumors the PR expressing cells were associated with elevated cell proliferation. In a second group the PR expression was not significantly associated with cell proliferation (33% of the cases). Finally, in 22% of the samples the cells carrying PR showed lower cell proliferation. We also detected lower ER immunoreactivity in 30% of the breast cancer biopsies with one of the monoclonal antibodies against ER (antibody 1D5 directed against the A/B domain). This group of tumors was PR-negative (or very weakly positive) and had high proliferation. The presence of tumors with abnormal ER proteins and displaying ER/PR significantly associated with elevated cell proliferation could have implications in human breast cancer treatment.     

Role of progesterone receptors in breast cancer

It has been demonstrated that progesterone receptors (PRs) are at least as valuable as estrogen receptors (ERs) for predicting outcome in breast cancer patients. Retrospective analysis indicates that the presence of PRs may be the second most critical factor, after the number of positive nodes, in predicting disease-free survival, with a correlation between length of survival and number of tumor PRs. The presence of PRs has been shown to be of value for predicting response in both early and advanced breast cancer patients. In studies of assay consistency, major discordance rates were minimal in simultaneous assays, but extremely high in sequential assays of tumors that were PR-positive in initial assay. The responsible factor was interim endocrine therapy, and it was subsequently determined that the prognosis was worse for those patients whose tumors lost PR between assays.     

p29 protein in breast cancer: relation between estrogen and progesterone receptors

An immunoradiometric assay was used to determine the presence of p29 protein in 68 breast cancer cyTOSOLS. The p29 values ranged from 0 to 1123 U/mg, with a mean value of 127 +/- 28.7 U/mg. Using a cutoff point of 20 U/mg the frequency of p29 positive tumors was about 55%. A quantitative and qualitative relation was found between p29 and estrogen receptor (ER), but not between p29 and progesterone receptor (PR). Discordance between p29 and ER status was found in 13 out of 68 tumors. Both the frequency of p29 positive tumors and the p29 values were significantly higher in postmenopausal than in premenopausal women, in a similar way to ER but different from PR. There was no difference in p29 content between primary tumor and metastasis. We did not find any relation among p29 primary tumors content and axillary lymph nodes involvement or tumor size.     

Estrogen and progesterone receptors as prognostic factors in breast cancer

The relation between estrogen receptors (ER) and/or progesterone receptors (PgR) and some clinical factors such as tumor size, axillary node involvement, histological tumor grade, and disease-free interval (DFI) in 500 patients with operable (TNM stage I-III) breast cancer was studied. ER-positive (ER+) tumors were commoner in older patients, whereas PgR-positive (PgR+) tumors were similarly distributed within the age groups. The concentration of ER+ protein also increased with age in contrast to PgR+ protein concentration. However, receptor status was not associated with menopausal status independently of age. Axillary node involvement influenced neither ER nor PgR status, but there was a statistically significant relation between tumor size and positivity of ER or PgR. There was no association between histologic tumor grade and either steroid receptor phenotype. DFI was longer in patients with ER+ than those with ER- tumors, independently of axillary nodal status. The positivity of PgR in patients with ER+ tumors contributed to an even longer DFI, suggesting that the combination of ER/PgR is a better indicator of DFI than ER or PgR alone.     

血清睾酮水平与乳腺癌雌、孕激素受体表达的相关性研究

目的:回顾性研究血清睾酮（testosterone,T）水平与乳腺癌雌激素受体（estrogen receptor,ER）,孕激素受体（progesterone receptor,PR）表达的相关性。方法:回顾性分析2016年1月至2018年12月在南京市妇幼保健院进行体检和治疗的63例健康女性,99例良性肿瘤,204例乳腺癌的临床病理资料,比较三组之间的血清睾酮水平的差异。将所有204例乳腺癌患者根据睾酮水平由低到高排序,按四分位数分为4组,采用Logistic回归比较不同睾酮水平下4组乳腺癌患者ER、PR、Her2表达状态的比值比（OR）。结果:乳腺癌组血清睾酮水平与乳腺良性肿瘤组、健康对照组相比差异均无统计学意义（P＞0.05）。ER+和PR+乳腺癌患者中血清睾酮水平分别高于ER-和PR-患者,而Her2+乳腺癌患者中血清睾酮水平低于Her2-患者,差异均有统计学意义（P＜0.05）。采用Logistic回归计算OR值,根据绝经与否进一步分层,其中T≥0.44 ng/mL组相对于T≤0.22 ng/mL组ER阳性表达的总体OR值为2.46（95%CI=1.04~5.86,P=0.042）,绝经前OR值为3.77（95%CI=1.11~12.80,P=0.034）,绝经后OR值为1.05（95%CI=0.28~3.92,P=0.945）;T≥0.44 ng/mL组相对于T≤0.22 ng/mL组PR阳性表达的总体OR值为3.69（95%CI=1.60~8.49,P=0.002）,绝经前OR值为4.80（95%CI=1.51~15.23,P=0.008）,绝经后OR值为1.78（95%CI=0.47~6.71,P=0.396）,结果显示绝经前乳腺癌患者中ER、PR的阳性表达与血清睾酮水平呈现出明显的正相关性;而Her2阳性表达与血清睾酮水平在总体、绝经前、绝经后乳腺癌患者中均未表现出明显的负相关性。结论:高血清睾酮水平与乳腺癌ER、PR的阳性表达呈正相关,在绝经前乳腺癌患者中表现尤为显著。血清睾酮水平可以作为预测绝经前激素受体状态的标志物之一。     

乳腺癌临床诊断中雌激素和孕激素受体表达的意义

目的探讨雌激素(ER)和孕激素(PR)受体的表达在乳腺癌临床诊断中的意义。方法选取2013年3月至2014年3月间大连大学附属中山医院收治的60例乳腺癌患者,另选取大连市红星社区体检健康人员60例为对照组。所有患者术前均进行ER和PR水平测定,分析彩色多普勒超声表现特征,采用免疫组织化学染色检测ER和PR在乳腺及其周围组织中的表达。结果年龄≥40岁的乳腺癌患者的雌二醇激素含量和孕酮激素含量均高于<40岁的患者,两者比较差异有统计学意义(P<0.05)。免疫组化反应测定中,与健康成年女性比较,乳腺癌患者ER和PR水平均高(均P<0.05),且集中分布于细胞质当中。乳腺癌肿块边缘性状和血流信号的分级与ER、PR均有统计学意义(均P<0.05)。结论年龄偏大,ER和PR水平高,彩色多普勒检查显示乳腺肿块边缘不清晰、周围组织血流不丰富,提示可能患有乳腺癌。     

Associated expressions of FGFR-2 and FGFR-3: from mouse mammary gland physiology to human breast cancer

Fibroblast growth factor receptors (FGFRs) are tyrosine kinase receptors which have been implicated in breast cancer. The aim of this study was to evaluate FGFR-1, -2, -3, and -4 protein expressions in normal murine mammary gland development, and in murine and human breast carcinomas. Using immunohistochemistry and Western blot, we report a hormonal regulation of FGFR during postnatal mammary gland development. Progestin treatment of adult virgin mammary glands resulted in changes in localization of FGFR-3 from the cytoplasm to the nucleus, while treatment with 17-β-estradiol induced changes in the expressions and/or localizations of FGFR-2 and -3. In murine mammary carcinomas showing different degrees of hormone dependence, we found progestin-induced increased expressions, mainly of FGFR-2 and -3. These receptors were constitutively activated in hormone-independent variants. We studied three luminal human breast cancer cell lines growing as xenografts, which particularly expressed FGFR-2 and -3, suggesting a correlation between hormonal status and FGFR expression. Most importantly, in breast cancer samples from 58 patients, we found a strong association (P?相似文献   

Immunohistochemical image analysis of estrogen and progesterone receptors in breast cancer

Background  Recently objective quantification of immunohistochemical estrogen receptor (ER) and progesterone receptor (PgR) staining in breast cancer by image cytometry has been predominantly performed by measuring the area of positively stained cells. However, in sample preparations of immunostained hormone receptors, both the stained area and the intensity of staining vary. In this study, we performed quantification of the stained area by measuring, tailing intensity using image cytometry. Methods  Quantitative analysis of ER and PgR immunohistochemistry was performed using image cytometry. The obtained values were presented as % of positive staining (%PS). Comparison of %PS with values obtained by EIA and with clinicopathological features was performed. Results  The %PS values and the natural logarithm of the EIA levels of the hormone receptors showed a significant positive correlation for both ER and PgR. The concordance of the results obtained by the two methods was 96.3% for ER and 73.7% for PgR. The ER-%PS values of postmenopausal patients were significantly higher than those of premenopausal patients, whereas the PgR-%PS values of the former group were significantly lower than those of the latter group. Conclusions  The quantification of ER and PgR in immunostained preparations using %PS as a parameter was reproducible and showed a high correlation with values obtained by EIA. It was shown that only menopausal status affects hormone receptor levels when analyzing the relationship between %PS measurements and clinicopathological features.     

Prognostic value of estrogen and progesterone receptors in primary breast cancer

Estradiol receptor alone or estradiol and progesterone receptors (ER, PgR) have been measured in tumors from 307 women who were treated for primary breast adenocarcinoma. Patients received adjuvant therapy in relation to tumor stage independently of receptor status. Over a relatively short follow-up, more recurrences are recorded in patients with ER+ tumors, but at 7 years the same proportion of recurrences are registered in both groups of patients whose tumors were ER+ or ER-. Patients whose tumors were processed for both ER and PgR (148 cases) have now been evaluated after 5 years follow-up. Among 56 patients with PgR+ tumors 5 recurred, versus 22/92 in the PgR- group. 21/87 patients who had 1 to 4 invaded nodes at the time of surgery relapsed: 17/54 had PgR- tumors versus 4/33 PgR+. 6 recurrences were recorded in the 61 patients with negative nodes: 5 of them occurred in patients with PgR- tumors. In addition, recurrences observed in patients with negative receptor status occurred after a shorter disease-free interval. Analysis of the incidence of recurrences in relation to the combined ER/PgR status in patients who did not receive adjuvant therapy suggests that tumor PgR content is a more significant criterion than ER for long-term prognosis.     

Estrogen, progesterone, and androgen receptors in breast cancer in the Japanese: brief communication

Estrogen, progesterone, and androgen receptors (ER, PgR, and AR, respectively) were determined by dextran-coated charcoal assay analyzed with Scatchard plots in cytosols from 81 Japanese patients with breast cancer. For the estimations of PgR and AR, the following compounds were used: a synthetic progestin, [3H]R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione), not bound by corticosteroid-binding globulin; and a synthetic androgen, [3H]R1881 (17beta-hydroxy-17-methylestra-4,9,11-trien-3-one), not bound by human sex steroid plasma-binding protein. Forty-two of 81 of the cancers revealed measurable amounts of ER (greater than 2 fmoles/mg cytosol protein), whereas the rates of measurable amounts of PgR (greater than 5) and AR (greater than 5) were 27% (18/67) and 36% (17/47), respectively. PgR were found in 45% of cancer patients with ER, but in only 9% of the cancer patients without ER. AR were found in 50% of the cancer patients with ER, but in only 22% of the cancer patients without ER. These results are consistent with those reported by Western investigators.     

Beta-adrenergic receptors in human breast cancer: identification, characterization and correlation with progesterone and estradiol receptors.

Besides the variety of other cellular processes in which beta-adrenergic compounds have been involved, their effect on the second messenger cAMP is thought to be related to the growth and differentiation of malignant cells. Because beta-adrenergic receptor could be an easy target for a new combination treatment, we attempted to identify and characterize adrenergic receptor in breast tumor and sought for correlations with estradiol and progesterone receptors. Using L[3H]-dihydroalprenolol, a potent beta-adrenergic antagonist, we demonstrated in human breast tumor the presence of beta-adrenergic receptors with high affinity (Kd 1-3 nM) as shown by Scatchard analyses. Natural and synthetic agonists and antagonists inhibited the [3H] DHA binding, mainly in the order of beta 2-subtype potency. We verified that these receptors were normally coupled with G-protein. A slight correlation was shown between adrenergic and progesterone receptors, and no correlation between adrenergic and estrogen receptors. The presence of specific beta-adrenergic receptors functionally coupled with G protein incited us to study their physiological regulation, since it is tempting to speculate that circulating or locally released catecholamines or other natural compounds may participate in the process of growth and differentiation of the mammary gland through adrenergic receptors.     

Oestrogen and progesterone receptors and disease-free interval in primary breast cancer.

Oestrogen and progesterone receptor assays were performed in 286 women with primary breast cancer, and the patient group was followed up for a minimum of 24 months. Of the 263 patients belonging to clinical stages I-III and serving as the population used for calculation of disease-free interval only 1.9% received postoperative endocrine treatment and 6.5% chemotherapy. No significant relationship between the presence or concentrations of oestrogen or progesterone receptor and the disease-free interval was observed. It is therefore possible that the positive relationship between these variables reported in some investigations reflects an influence by adjuvant endocrine measures.     

Estradiol and progesterone receptors in breast cancer: Prognostic value after relapse

Summary The prognostic significance of estradiol (ER) and progesterone receptors (PgR) for survival from relapse has been studied in two groups of breast cancer patients: group 1, 35 patients in whom receptor levels were measured at the time of mastectomy; group II, 49 patients in whom receptor levels were measured at the time of recurrence. ER + (>10 fmoles/mg) patients had a better survival from relapse than ER — patients. High levels of PgR (>50 fmoles/mg) had a prognostic significance only in group II patients.     

Ornithine decarboxylase activity, prolactin blood levels, and estradiol and progesterone receptors in human breast cancer

Ornithine decarboxylase (ODC) activity in human breast cancer tissues was correlated with prolactinemia (Prl), estradiol and progesterone cytosol receptors (ER and PR), and histopathologic pattern. Ninety-two cases of breast cancer, six benign mammary disease, and three normal breast tissues were studied for ER, PR, and ODC. Prolactinemia was assessed in 59 cancer patients, 14 of whom showed hyper-Prl along with significantly higher ODC than in patients with normal-Prl [(20.01 +/- 6.33) 10(-2) vs (5.20 +/- 0.90) 10(-2) pmol CO2/micrograms protein/h; P less than 0.0125]. A direct correlation was found between Prl and ODC in postmenopausal women (n = 40). Prl was assayed in seven of 13 ER-PR breast cancer patients; a highly significant, direct correlation was found between Prl and ODC in this group (r = 0.934, P less than 0.0025). ODC did not correlate with ER or PR. Carcinomas with higher ODC (n = 17) had higher cellularity, lower histologic differentiation, and higher nuclear anaplasia than those in which ODC was not detectable (n = 13). In normal breast and five of six benign mammary disease tissues, ODC was not detectable. These findings suggest that ODC could be a reliable marker for prognosis.     

Estrogen and progesterone receptors in human breast cancer with concomitant assay of plasma 17beta-estradiol, progesterone, and prolactin levels.

The specific estrogen receptor in the cytosol of human breast cancer tissue was assayed in 217 primary cases. The specific progesterone receptor was also assayed in 48 cases as evidence of estrogen action on the tissue. Both receptors were positive in 45.8% of all cases. Plasma 17beta-estradiol and progesterone were assayed concomitantly with these steroid receptors. The higher hormone levels were found in the cases with fewer receptor binding sites. The relationship between 17beta-estradiol levels in tumor cytosol and the number of binding sites was more clearly observed. Plasma prolactin levels, however, showed no correlation with the number of receptor binding sites or the plasma levels of sex steroids. None of these assayed substances had a clear correlation with the histological type of tumor or the clinical stage of the disease.     

Expression of estrogen,progesterone and epidermal growth factor receptors in primary and metastatic breast cancer

The prognostic value of epidermal growth factor receptor (EGFR) expression and its biological role in estrogen receptor-positive (ER⁺) and ER-negative (ER^?) primary breast cancer is controversial. In this study, distributions of ER, progesterone receptor and EGFR have been established using immunohisto-chemistry in both primary breast tumors and their matched axillary lymph node metastases of 26 patients or their matched distant metastases of 2 patients. In addition, 5 patients with bilateral breast cancer were studied. ER⁺ tumor cells were detected in 22 (69%) and EGFR⁺ tumor cells were detected in 11 (34%) primary breast carcinomas. Expression of ER and EGFR was inverse regarding the individual tumor cells in both primary tumors and metastases. Relationship of EGFR expression with poorly differentiated and large breast tumors was observed. Furthermore, primary tumors with a predominant lobular component were ER⁺ and, with one exception, EGFR^?. Invasive ductal carcinomas were more frequently EGFR⁺. No apparent differences in receptor expression were observed between primary tumors and lymph node metastases or chro-nously or metachronously occurring bilateral breast cancers. Only one ER⁺ primary tumor showed a switch to EGFR expression in the involved lymph node. Our study shows that a shift in receptor phenotype between primary tumors and lymph node metastases is a rare event and, thus, additional analyses of involved lymph nodes will not likely serve as a better predictor for response to anti-estrogen therapy. We conclude that expression of EGFR is not a prerequisite for development of metastases. © 1995 Wiley-Liss, Inc.