Estrogen Receptor Assay (ER, Estradiol Receptor)

Sample
- Breast cancer tissue blocks are needed.
Purpose of the test
- ER is done on the breast cancer tissue to evaluate the hormone response.
- ER also gives an idea about the prognosis.
Pathophysiology
- The estrogen receptor is a specific cellular protein with high affinity and specificity for Estrogen hormone.
- The estrogen receptor protein is found in the target tissue like the breast, uterus, pituitary gland, and hypothalamus.
- Estrogen stimulates the cells through the Estrogen receptor.
- A reduction in the blood estrogen level reduces the biochemical activity of these cells.
- This is the basis for the treatment of breast cancer by anti-hormone therapy,
- ER, positive breast cancer is twice more responsive than ER-negative cases.
- Postmenopausal women breast cancers are more ER-positive than young women.
- ER, positive tumors have a better prognosis than ER-negative cases.
- More than 50% of the ER-positive cases respond to anti-hormone therapy (Tamoxifen).
- Metastatic carcinoma of the breast, 1/3 of the women has various types of endocrine therapy directed as lowering their estrogen level e.g.
- Oophorectomy.
- Hypophysectomy.
- Adrenalectomy (ablation therapy).
- Anti-estrogen and androgen (additive therapy).
- False-negative ER-receptor is:
- Incorrect handling and storage of tissue samples leading to thermolabile receptor protein degradation.
- If there is low protein concentration in the assayed sample.
- If a biopsy is taken from the surrounding normal tissue.
- PR- receptor is useful to help to the assay of the ER-receptors.
- Metastatic cancer with ER and PR receptor-positive tumors have a response rate of 75% to endocrine therapy.
- If the ER-positive and PR negative tumors have a 40% response rate.
- If ER-negative and PR-positive patient’s only response rate is 25% for endocrine therapy.
- In the case of ER and PR negative, the response rate is only 5%.
- The percentage of positive cases in postmenopausal women is greater than the premenopausal women.
Procedure for ER
- Mostly ER is done on the cancer tissue paraffin blocks as immunohistochemistry.
- Another method can be an enzyme immunoassay.
- Chromatography techniques.
- EIA.
- Reading of the immunocytochemistry slides:
- Negative = < 5 % of the cells nuclei for the receptors.
- Positive = > 5 % of the cells nuclei stain for the receptors.
Clinical evaluation
- Carcinoma of the breast 60% shows positivity.
- Approximately 2/3 of the cases show a response to hormone therapy.
- In ER-negative cases, 90% do not respond to hormone therapy.
- The hormone receptor positivity varies in different patients:
- ER+ = 80% of the cases.
- ER+ PR+ = 65% of the cases.
- ER+ PR- = 13% of the cases.
- ER- PR+ = 2% of the cases.
- ER- PR- = 25% of the cases.
Interpretation
- Favorable response >20 % cell stain.
- The borderline response is 11 to 20 % of the cell stain.
- The unfavorable response is < 10 % cell stain.
- ASCO guideline is:
- Positive for ER/PR if ≥ 1% of the tumor cell nuclei are immunoreactive.
- Negative ER/PR if <1% of tumor cells nuclei are immunoreactive.
- Allred scoring: This replaced the early scoring system.
- ER-positive tumor cells have > 10% positive cells.
- ER-negative tumor cells are 1 to 9% positive cells.
- ER-positive tumor cells have > 10% positive cells.
Score | Positive cells % | Intensity | Intensity score |
0 Score | o | None | 0 |
1 | None | Week | 1 |
2 | 1 to 10 | Intermediate | 2 |
3 | 11 to 33 | Strong | 3 |
4 | 34 to 66 | ||
5 | 66 to 100 |
- Progesterone receptors (PR) should be done along with the ER. Because PR depends upon the estrogen activity.
- PR positivity confirms that all the steps for the ER are done correctly.
- When ER / PR positive then the response of the tumor is 75 % to the treatment.
Response to anti-hormone therapy
ER | PR | Response to hormones |
---|---|---|
positive | positive | 75 % |
negative | positive | 60 % |
positive | negative | 35 % |
negative | negative | 25 % |