Estrogen receptor test

The ER activity can be monitored using immunohistochemical methods in applications like tissue analysis for tumorigenesis. The activation of the ER through binding to the estrogen hormone stimulates mammary cell division, catalyzing cell division and DNA replication processes. This results in exponential multiplication the mutated genes, along with large amounts of genotoxic waste, which in turn highly increase the chances of malignant cell formation and the likelihood of tumor formation.

There are two main types of estrogen receptors: estrogen receptor alpha (ERα) also known as NR3B1, and estrogen receptor beta (ER-β) also known as NR3A2. Both are nuclear receptors activated by the sex hormone estrogen and encoded by the ESR1 (Estrogen Receptor 1) gene. The estrogen signaling can be stimulated or inhibited selectively. This depends upon the equilibrium of these two receptor types in target organs.[2]

These two ER types are encoded by different genes located on separate chromosomes and have different functions. ERα is mostly active in the mammary gland and uterus, and aids in the regulation of skeletal homeostasis and metabolism.[3] ER-β on the other hand, plays a more prominent role in the central nervous and immune systems functional mechanisms.[3]

The ERT immunohistochemical assessment is a semi-quantitative method used to predict the likelihood of success to anti-estrogen therapy in breast carcinoma. ER-positive breast carcinomas are likely to respond to various endocrine treatments. Therefore, monitoring ER activity can be essential in disease and treatment progression.

Various target antibodies may be used in the IHC assessment of the ER. Typically, the antibody used for this experiment is the anti-Estrogen Receptor (ER) (SP1) Rabbit Monoclonal Antibody. Employing SP1 allows for detecting estrogen receptor (ER) antigens in sections of the fixed patient samples. In junction with light microscopy, the approximate ER activity can be estimated using the level of staining of the cell's components. The anti-ER (SP1) antibody targets the ER alpha protein (ERα) located in the nucleus of ER-positive normal and neoplastic cells.[4] The anti-ER (SP1) antibody's response is a useful indication of the progression, management, and prediction of therapy outcome of breast cancer. These antibodies are commercially available from 3 commonly used auto strain vendors- Dako, Leica, and Ventana. In a study by Kornaga et al, all behaved similarly in the semi-quantitative analysis of breast cancer biopsy samples.[4]

In a study in 2002, 6 breast carcinoma cases were received, characterized, and analyzed through the ERT IHC assessment. The level of known ER activity was classified (negative, low, medium, and high) and selected for observation. After embedment in a paraffin block, the samples were stained using a hematoxylin and eosin staining (H & E staining) system. The IHC analysis was then performed the same day using anti-ER monoclonal antibodies, and resulted in a consistently strong correlation in the carcinoma samples with ER activity. In contrast, the level of ER activity increased, while the IHC response increased respectively.[5]

A major challenge in cancer diagnosis and treatments is that the symptoms of many cancers are easily ignored or incorrectly credited to other ailments. The monitoring of irregularities or changes in receptor functions and be particularly useful in such cases.

Predictive biomarker assays seem to be the current gold standard for therapeutic interventions as they allow quantitative insights into the molecular environment. The estrogen receptor (ER) is no exception, as the observation of this receptor’s activity allows for insight into growth and proliferation and allows for differentiations to be made between various intercellular environments. The complex biochemical reactions of estrogen receptors are necessary for the mediation of cellular interactions in response to various cell-altering factors, including ligands, cofactors, and other simulative complexes.[6]

Monitoring tumor development with the estrogen receptor test

Tumor Growth

The estrogen receptor is a regulator of cellular functions, including cell growth and proliferation, and can serve as a means of inter-cellular differentiation.[6] Monitoring the activity of the ER via the ERT is necessary as it plays an essential role in normal breast development and function, as well as in cancerous situations. Accurate measurements of the ER activities are critical in the care and progression monitoring of breast cancers as the ER can serve as an indicative biomarker as it is a potential predictor for the clinical responses of a patient to cancer treatments. It has been proven that breast cancer patients who present an ER-positive status are most likely to respond to cancer treatments through endocrine therapy.[7] Measuring the ER activity is essential in the care of breast patients as the Estrogen receptor test allows for informed decisions to be made for the future best treatments for cancer patients.

Estrogen Receptor Pathway

The schematic models the activity pathway of the estrogen receptor.

In the typical estrogen pathway (i) estrogen or other selective estrogen receptor modulators (SERMs) are bound to the estrogen receptor (ER) via the coregulatory proteins (CoReg) in the nucleus.[8]

Alternately, the estrogen or SERM complexes may occur through the ER located adjacent to the plasma membrane (ii) with the help of adaptor proteins such as caveolin 1 or SHC1, which target the ER complexes to the plasma membrane.[8] Activation of the ER complex causes increased kinase activity in phosphoinositide 3-kinases (PI3K) and mitogen-activated protein kinase (MAPK) as well as increases in concentrations of signaling molecules like calcium and nitric oxide.[8]