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Estrogen Receptor Assay (ER, Estradiol Receptor)

Estrogen Receptor Assay (ER, Estradiol Receptor)
September 18, 2020Lab TestsTumor marker

Sample

  • Breast cancer tissue blocks are needed.

Purpose of the test

  1. ER is done on the breast cancer tissue to evaluate the hormone response.
  2. ER also gives an idea about the prognosis.

Pathophysiology

  1. The estrogen receptor is a specific cellular protein with high affinity and specificity for Estrogen hormone.
    1. The estrogen receptor protein is found in the target tissue like the breast, uterus, pituitary gland, and hypothalamus.
  2. Estrogen stimulates the cells through the Estrogen receptor.
  3. A reduction in the blood estrogen level reduces the biochemical activity of these cells.
  4. This is the basis for the treatment of breast cancer by anti-hormone therapy,
    1. ER, positive breast cancer is twice more responsive than ER-negative cases.
  5. Postmenopausal women breast cancers are more ER-positive than young women.
  6. ER, positive tumors have a better prognosis than ER-negative cases.
  7. More than 50% of the ER-positive cases respond to anti-hormone therapy (Tamoxifen).
  8. Metastatic carcinoma of the breast, 1/3 of the women has various types of endocrine therapy directed as lowering their estrogen level e.g.
    1.  Oophorectomy.
    2. Hypophysectomy.
    3. Adrenalectomy (ablation therapy).
    4. Anti-estrogen and androgen (additive therapy).
  9. False-negative ER-receptor is:
    1. Incorrect handling and storage of tissue samples leading to thermolabile receptor protein degradation.
    2. If there is low protein concentration in the assayed sample.
    3. If a biopsy is taken from the surrounding normal tissue.
  10. PR- receptor is useful to help to the assay of the ER-receptors.
    1. Metastatic cancer with ER and PR receptor-positive tumors have a response rate of 75% to endocrine therapy.
    2. If the ER-positive and PR negative tumors have a 40% response rate.
    3. If ER-negative and PR-positive patient’s only response rate is 25% for endocrine therapy.
    4. In the case of ER and PR negative, the response rate is only 5%.
  11. The percentage of positive cases in postmenopausal women is greater than the premenopausal women.

Procedure for ER

  1. Mostly ER is done on the cancer tissue paraffin blocks as immunohistochemistry.
  2. Another method can be an enzyme immunoassay.
  3. Chromatography techniques.
  4. EIA.
  5. Reading of the immunocytochemistry slides:
    1. Negative = < 5 % of the cells nuclei for the receptors.
    2. Positive = > 5 % of the cells nuclei  stain for the receptors.
ER/PR receptor presentation

ER/PR receptor presentation

Clinical evaluation

  1. Carcinoma of the breast 60% shows positivity.
  2. Approximately 2/3 of the cases show a response to hormone therapy.
  3. In ER-negative cases, 90% do not respond to hormone therapy.
  4. The hormone receptor positivity varies in different patients:
    1. ER+ = 80% of the cases.
    2. ER+ PR+  = 65% of the cases.
    3. ER+ PR-  = 13% of the cases.
    4. ER-  PR+  = 2% of the cases.
    5. ER-  PR-  = 25% of the cases.

Interpretation

  1. Favorable response >20 % cell stain.
  2. The borderline response is 11 to 20 % of the cell stain.
  3. The unfavorable response is < 10 % cell stain.
  4. ASCO guideline is:
    1. Positive for ER/PR if  ≥ 1% of the tumor cell nuclei are immunoreactive.
    2. Negative ER/PR if  <1% of tumor cells nuclei are immunoreactive.
  5. Allred scoring: This replaced the early scoring system.
    1. ER-positive tumor cells have > 10% positive cells.
      1. ER-negative tumor cells are 1 to 9% 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
  1. Progesterone receptors (PR) should be done along with the ER. Because PR depends upon the estrogen activity.
  2. PR positivity confirms that all the steps for the ER are done correctly.
  3. 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 %
Brown color indicates positive reaction (ER+)

Brown color indicates a positive reaction (ER+)


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