Estrogen Receptor (ER) Antibody Review

Introduction

a useful immunohistochemical marker of breast carcinomas and is commonly used as a means of distinguishing breast carcinomas from adenocarcinomas of other primary sites. PMID: 16540736
estrogen receptor (ER) status and, to a lesser extent, progesterone receptor status have been recommended by recently published guidelines as important for routine prognostic and predictive evaluation of breast cancer. PMID: 16491599, PMID: 15726618
Breast cancer estrogen-receptor (ER) status is useful in predicting benefit from endocrine therapy and advances in adjuvant chemotherapy. PMID: 16609087, PMID: 16596655, PMID: 16541305, PMID: 15069113
mediating estrogen-signaling stimuli, is a dominant regulator and a key therapeutic target in breast cancer etiology and progression. PMID: 16273359
a regulator of cellular growth, proliferation, and differentiation. In addition to having prognostic value, ER is the most important biologic marker of therapeutic response in breast cancer. PMID: 15614160
ER is present in more than half of breast tumors, this receptor has been the most widely targeted protein in breast cancer therapy. PMID: 15052541

Normal Expression

ER is mainly nuclear but it is also present in the cytoplasm. PMID: 1988286
Some level of measurable ER protein is expressed in 70-80% of human breast. PMID: 15614160
ER are present in both lactotropes and gonadotropes. PR are present in gonadotropes, but not lactotropes, of the primate pituitary. PMID: 2492931
Estrogen receptor-immunoreactive cells are found in midbrain sites previously reported, including the midbrain central gray, the tegmentum lateral and ventral to the central gray, peripeduncular region, and parabrachial nuclei. PMID: 8429127
Dopamine-beta-hydroxylase-immunoreactive (DBH-IR) varicosities were closely associated with ER-IR cells throughout the hypothalamus and preoptic area. PMID: 1842698
AR- and ERbeta-immunopositive cells were present in SNR and SNC in both sexes and at all ages. PMID: 12435407
ER was found as a red nuclear staining in the surface, crypt, and glandular epithelium; in endometrial stroma cells; and in smooth muscle cells of the tunica muscularis of the uterus. Total scores of ER-positive cells varied during the estrous cycle, with the highest scores in the early proliferative stage and the lowest scores in the early secretory stage of the estrous cycle. These results are in concordance with the observations in other animals and the human uterus. In the canine ovaries, positive staining for ER was present in surface epithelium and subsurface epithelial ingrowths, which is in contrast with negative staining of human ovaries. PMID: 9171972
In uterus and vagina, ER was recognized in nuclei of epithelial cells, stromal cells and smooth muscle cells of the muscle layer and blood vessels. Liver tissue showed positive nuclear immunostaining in parenchymal cells; however, no reaction was present in endothelial cells, Kupffer cells, bile ductal cells, and smooth muscle cells of blood vessels. ER was localized in the nuclei of anterior pituitary cells while weak reaction was also recognized in cells of the intermediate lobe. No staining was detected in the posterior pituitary. Results demonstrate that both occupied and unoccupied ER are localized in the cell nucleus from several target tissues. PMID: 2654099
ER expression was observed in both the nuclei and cytoplasm of gallbladder epithelium in 12 of 29 specimens. PMID: 16291158
estrogen receptors (ERs), mainly ERb, are present and functional in normal lung and tumor cell lines and tissues. PMID: 15161576
All meibomian glands had positive nuclear staining with antibodies for estrogen receptors in their outer cell layers, i.e., the basal cell layer. The proportion of cells expressing estrogen receptors increased with age independent of gender. PMID: 12904971
Both ER types were expressed in numerous sensory neurons of either upper lumbar (L1/L2) or lower lumbar/sacral (L6/S1) ganglia and there was almost complete coexpression of ERalpha and ERbeta. ER-positive neurons were mainly small-medium size (18-25-microm diameter), indicating that they may be nociceptors and/or supply visceral targets. PMID: 12798205

Abnormal Expression

ER positive immunostaining (81 of 115) was always located in the nucleus of tumor cells and of normal cells in adjacent breast tissue. PMID: 3524808
estrogen receptors were observed in tumor cells (serous papillary adenocarcinoma of the endometrium) forming papillary structures but not in the tumor cells of the solid, more poorly differentiated areas. PMID: 1690076
In non-malignant region, ER mRNA and ER protein were found in cytoplasm and nucleus, respectively, of stromal cells, but not in glandular epithelial and basal cells. In benign regions, ER mRNA/ER protein positive cells were found in fibromyoadenomatous and myoadenomatous hyperplasia, but not in adenomatous hyperplasia. PMID: 7501542
overwhelming majority of breast cancers are either completely ER- or unambiguously ER+, and cases with weak ER immunostaining are rare. PMID: 15762275
most uterine leiomyosarcomas (LMS) coexpress ER and PR, and most extrauterine LMS do not stain for these antigens. However, a subset of extrauterine LMS are ER and/or PR immunoreactive. PMID: 15536333
In Myasthenia gravis (MG) patients, we found an increased expression of ER alpha on thymocytes and both ERs on T cells from peripheral blood mononuclear cells, indicating that the signals provided by thymic and peripheral microenvironments are distinct. Finally, activation of normal thymocytes by proinflammatory cytokines induced increased expression of ERs especially in the CD4+ subset, suggesting that an excess of proinflammatory cytokines could explain the increase of ERs expression on MG lymphocytes. PMID: 15661863

Expression Alteration

present result extend our previous work (Yokosuka and Hayashi, 1992) showing that the expression of the ER in the facial nucleus is transient. PMID: 7842523
bilateral ovariectomy in guinea pig lead to severe osteoarthritis which mighgt be related to the lower serum level of estrogen and the downregulation of the expression of ER in the cartilage also. PMID: 16696325
significantly increased expression of estrogen receptor correlated with the severity of facet arthritis. PMID: 15738791

Function

10 % staining proportion may be an acceptable cut-off point for both ER and PR status by IHC, in terms of predicting response to endocrine therapy in breast cancer. PMID: 15550845
The results in male mice, with prior findings in female mice, 1) demonstrate estrogen receptors have a smaller effect on alveolar dimensions in male than female mice, 2) show ER-alpha and ER-beta are required for the sexual dimorphism of alveolar size, and 3) show ER-alpha is needed for the sexual dimorphism of body mass-specific alveolar number and surface area. PMID: 16361355
modulate cholangiocyte proliferation and play a role in tumorigenesis of estrogen-dependent malignancies and in the proliferation of gallbladder epithelium. PMID: 16291158
ER immunostaining could be very useful in distinguishing between serous carcinomas and peritoneal mesotheliomas. PMID: 16260268
inhibiting the action of the estrogen receptor (ER) represents one of the earliest examples of a successful targeted therapy for clinical breast cancer. PMID: 15687641
Estrogen receptor (ER)-positive breast cancers generally have a better prognosis and are often responsive to anti-estrogen therapy, which is the first example of a successful therapy targeted on a specific protein, the ER. Unfortunately ER-negative breast cancers are more aggressive and unresponsive to anti-estrogens. PMID: 12790787

Applications

ELISA

Development of two ELISA for estrogen and progesterone receptor with sufficient sensitivity for fine needle aspirate and core biopsy. PMID: 11344529
Fluorometric ELISA method for rapid screening of anti-estrogen receptor antibody production in hybridoma cultures. PMID: 4067317

Electron Microscopy (EM)

Estrogen receptor-immunoreactive glia, endothelia, and ependyma in guinea pig preoptic area and median eminence: electron microscopy. PMID: 1727710
Immuno-electron microscopic identification of human estrogen receptor-DNA complexes at the estrogen-responsive element and in the first intron of a Xenopus vitellogenin gene. PMID: 3216393
localization and quantitative changes of estradiol receptor (ER) were studied by means of immunogold-electron microscope methods using a polyclonal antibody directed against an amino acid sequence representing the DNA binding site of ER. PMID: 1988286
Estrogen receptor immunocytochemical assay (ER-ICA): computerized image analysis system, immunoelectron microscopy, and comparisons with estradiol binding assays in 115 breast carcinomas. PMID: 3524808
Immunoelectron microscopic localization of estrogen receptor with monoclonal estrophilin antibodies. PMID: 4020102

Enzyme Immuno Assay (EIA)

estrogen receptor (ER) was measured by isoelectric focusing (IF) and enzyme immuno assay (EIA) in 127 breast cancer samples. PMID: 3020880

Flow Cytometry (FC)

Flow cytometric analysis of estrogen receptor expression in isolated nuclei and cells from formalin-fixed paraffin-embedded archival mammary cancer tissues. PMID: 10554161
Flow cytometric analysis of estrogen, progesterone receptor expression and DNA content in formalin-fixed, paraffin-embedded archival human breast tumors. PMID: 10323218
Dynamic changes in estrogen receptor levels in the cell cycle of human endometrial adenocarcinoma studied by flow cytometry. PMID: 2433371
Estrogen receptor analysis by flow cytometry. PMID: 6719116
Image and flow cytometric analysis of DNA content in breast cancer. Relation to estrogen receptor content and lymph node involvement. PMID: 6732072
Flow cytometry of breast carcinoma: II. Relation of tumor cell cycle distribution to histology and estrogen receptor. PMID: 7272941
Flow cytometry of breast carcinoma: I. Relation of DNA ploidy level to histology and estrogen receptor. PMID: 7272940
Measurement of estrogen receptors in intact cells by flow cytometry. PMID: 11002266
Immunocytochemical detection of estrogen receptors in bone cells using flow cytometry. PMID: 9099995
Flow cytometric determination of estrogen receptors in intact cells. PMID: 6722791
expression of estrogen receptors was evaluated at the protein level by flow cytometry, and at the mRNA level by polymerase chain reaction. PMID: 16197988
CD4+ helper T cells expressed higher level of ERs, compared with CD8+ cells, as assessed by flow cytometry in thymocytes and peripheral blood mononuclear cells. PMID: 15661863

Immunocytochemistry (ICC)

Immunocytochemical determination of estrogen and progesterone receptors and flow cytometric DNA analysis of breast cancer on fine needle aspirates. PMID: 8135480
Immunocytochemical determination of estrogen and progesterone receptors on 50 fine-needle samples of breast cancer. A prospective study including biochemical correlation and DNA flow cytometric analysis. PMID: 1546694
Optimization of estrogen receptor analysis by immunocytochemistry in random periareolar fine-needle aspiration samples of breast tissue processed as thin-layer preparations. PMID: 16932030
Estrogen and progesterone hormone receptor status in breast carcinoma: comparison of immunocytochemistry and immunohistochemistry. PMID: 11892015
immunocytochemistry (ICC) with monoclonal antibodies to the estrogen receptor (ER) to localize ER in the oviducts, uteri, and cervix of untreated, estrogen-treated, and estrogen-progestin-treated spayed macaques. PMID: 3665848
Optimal fixation conditions for immunocytochemical analysis of estrogen receptor in cytologic specimens of breast carcinoma. PMID: 14968416
objective of the current study was to compare ICC evaluation of ER status on FNA smears by three methods. PMID: 14648786
Use of cultured cells as a control for quantitative immunocytochemical analysis of estrogen receptor in breast cancer. The Quicgel method. PMID: 10078107
Immunocytochemical detection of estrogen receptor in the facial nucleus of the newborn rat by three antibodies with distinct epitopes. PMID: 7729822
We investigated the use of the SAMBA 4000 image analysis system for quantitation of immunocytochemical ER content in 23 cases and PR content in 20 cases of breast carcinoma after obtaining cytology specimens by fine needle aspiration (FNA). PMID: 8397648
the first report to demonstrate the presence of ER immunohistochemically, and our results suggest the heterogeneity of ER expression among osteoblastic cells. PMID: 8237480

Immunohistochemistry (IHC)

we review studies addressing interlaboratory variability and recommend optimal testing techniques and reporting procedures for ER testing, with the goal of increasing interlaboratory standardization for ER analysis by immunohistochemistry. PMID: 15614160
1D5 and 6F11: An immunohistochemical comparison of two monoclonal antibodies for the evaluation of estrogen receptor status in primary breast carcinoma. PMID: 15842054
Measurement of estrogen receptor status by immunocytochemistry in paraffin wax sections. PMID: 16491599
Rabbit monoclonal antibody SP1 yields the same results as the well-known, standardized mouse monoclonal antibody to estrogen receptor (clone 1D5). Antibody affinity of SP1 is 8 times higher than that of 1D5. Thus, SP1 may prove of great value in the assessment of estrogen receptor status in human breast cancer. PMID: 15722800
Solving the dilemma of the immunohistochemical and other methods used for scoring estrogen receptor and progesterone receptor in patients with invasive breast carcinoma. PMID: 15565575
Estrogen and progesterone receptor contents (ER, PR) were assessed by an immunohistochemical method and DNA ploidy and S-phase by flow cytometry in frozen endometrial cancer tissue sections from 39 cases. PMID: 11578402
Pressure-cooking should be recommended as the method of choice for standardization of the ER immunohistochemical reaction. PMID: 16273191
Immunohistochemical determination of estrogen and progesterone receptors in human breast carcinoma. Correlation with histopathology and DNA flow cytometry. PMID: 2649227
Frozen tissue from 78 cases of endometrial adenocarcinoma was examined for the presence of estrogen (ER) and progesterone receptors (PgR) with specific monoclonal anti-receptor antibodies and the peroxidase-antiperoxidase method. PMID: 8898164
ER can be detected in routine tissue sections processed with antigen retrieval and ER1D5, and can be relied upon to provide accurate prognostic information regarding response to endocrine therapies in breast cancer patients. PMID: 8640700
Recently, several anti-estrogen receptor (ER) antibodies have appeared which can be successfully employed to assay routinely prepared tissue sections if used in conjunction with new antigen-retrieval techniques such as the microwave oven and citrate buffers. PMID: 7823585
immunocytochemical reactions were performed in paraffin sections of tissue samples from 62 patients with ductal mammary carcinoma using monoclonal antibodies against ER and pS2. PMID: 11374797
MW-irradiation enhanced ICC detectability of ER in frozen sections by greatly reducing the amount of ER extracted during the various washes used during normal ICC processing. PMID: 7649110
Immunocytochemical assay for estrogen receptor with monoclonal antibody D753P gamma in routinely processed formaldehyde-fixed breast tissue. Comparison with frozen section assay and with monoclonal antibody H222. PMID: 8490902
Comparison of estrogen receptor immunocytochemical assay in frozen and paraffin sections. PMID: 1590893
we examined primary lung adenocarcinomas with monoclonal antibodies to two different clones to ER (clone 6F11 and clone 1D5). Nuclear ER was seen only with the 6F11 clone, in 56% of the bronchioalveolar type and 80% of the no special type. No nuclear ER was seen in carcinomas utilizing the 1D5 clone. PMID: 11845849
IHC is superior to the LBA for assessing ER status in primary breast cancer because it is easier, safer, and less expensive, and has an equivalent or better ability to predict response to adjuvant endocrine therapy. PMID: 10334533
Immunohistochemistry of estrogen receptor protein in paraffin sections. Effects of enzymatic pretreatment and cobalt chloride intensification. PMID: 2459958
Immunohistochemical identification of basal-type cytokeratins in invasive ductal breast carcinoma--relation with grade, stage, estrogen receptor and HER2. PMID: 16334976
Immunohistochemical determination of estrogen and progesterone receptor positivity in uterine adenosarcoma. PMID: 15196864
Interobserver agreement for estrogen receptor immunohistochemical analysis in breast cancer: a comparison of manual and computer-assisted scoring methods. PMID: 15129906
minimum formalin fixation time for reliable immunohistochemical ER results is 6 to 8 hours in our laboratory, regardless of the type or size of specimen. PMID: 12866377
Assessment of interlaboratory variation in the immunohistochemical determination of estrogen receptor status using a breast cancer tissue microarray. PMID: 12090420
Immunohistochemical analysis of estrogen receptors in breast carcinomas using monoclonal antibodies that recognize different domains of the receptor molecule. PMID: 11127919
A new immunohistochemical antibody (1D5) for the assessment of estrogen receptor status on routine formalin-fixed tissue samples. PMID: 7890280
Biologic significance of quantitative estrogen receptor immunohistochemical assay by image analysis in breast cancer. PMID: 8042582

Western Blot (WB)

Western blot analysis and flow cytometric analysis of estrogen and progesterone receptors in fixed breast cancer cells. After fixed with 0.25% paraformaldehyde and 75% ethanol, breast cancer cells can be used for not only quantitative measurement of ER and PR, but also Western blot analysis of ER and PR. PMID: 15025971
A Western blot and molecular genetic investigation of the estrogen receptor beta in giant cell arteritis. PMID: 16859590
ERPC can be used to detect functional estrogen receptor expression in both Western blot and immunohistochemistry. PMID: 16153014