Estrogen receptor

Topic Completed: 1 June 2005

Revised: 12 April 2019

Revised: 18 January 2019

Copyright: (c) 2002-2019,, Inc.

PubMed Search: Estrogen receptor [title]

Nat Pernick, M.D.
Page views in 2018: 7,307
Page views in 2019 to date: 6,483
Cite this page: Pernick N Estrogen receptor. website. Accessed September 17th, 2019.
Definition / general
  • See also Breast malignant topic
  • Two subtypes: ER-alpha and ER-beta
  • ER-alpha:
    • "Classic" functions of ER
    • May render breast epithelium susceptible to proliferative stimulation of estrogen
    • Expressed in breast and endometrium
  • ER-beta:
    • "Housekeeping" functions
    • Expressed in normal ovary and granulosa cells
    • Carcinoma of breast, colon, prostate
  • Both alpha and beta share highly conserved DNA binding domain and commonly interact with estrogen-regulating factors, but may affect different genes
  • Presence of estrogen (type alpha) and progesterone receptors correlates best with response to anti-estrogen treatment (tamoxifen or others) or chemotherapy, only weakly with prognosis
    • Presence is associated with better differentiated tumors, older age
  • Evaluate % of tumor nuclei stained and intensity of staining (none, weak, moderate, strong)
  • Immunostaining now done on paraffin fixed tissue (previously required fresh tissue)
  • Metastases to skin are often positive for androgen receptor, even if ER-, PR- (Mod Pathol 2000;13:119)
  • Antigen retrieval techniques are required for ER if glyoxal fixative is used (Hum Pathol 2004;35:1058)
  • Compared to ER, PR staining adds only a limited amount of additional predictive information for response to hormonal therapy (Mod Pathol 2004;17:1545)
  • Nuclear stain
  • Cytoplasmic staining only is a negative result
Uses by pathologists
  • In breast cancer, predicts response to tamoxifen or other anti-estrogens
    • Also prognostic marker for survival (ER+ is favorable)
  • Relatively specific for breast origin (but numerous exceptions)
  • Distinguishes endocervical (ER-) from endometrial (ER+) adenocarcinomas (Am J Surg Pathol 2002;26:998)
Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Andrey Bychkov, M.D., Ph.D.,
Kameda Medical Center

Breast, mucinous carcinoma

Contributed by
Leica Microsystems

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Invasive ductal carcinoma, intense nuclear staining

Images hosted on other servers:
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Metastatic lobular carcinoma, breast

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Papillary urothelial carcinoma, bladder

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Breast carcinoma metastatic to stomach

Positive staining - disease
  • Breast carcinoma (varies by subtype and tumor grade) - well differentiated tumors are typically positive
  • Endometrial adenocarcinoma (75%)
  • Ovarian serous, mucinous and endometrioid adenocarcinoma (Am J Surg Pathol 2001;25:667), papillary urothelial carcinoma of bladder (10 - 20%) and ovarian transitional cell carcinoma (90%, Arch Pathol Lab Med 2005;129:194)
Negative staining
  • Endocervical adenocarcinoma, ovarian clear cell carcinoma
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