Oestrogen receptor (ER)

Specific staining occurs in the nucleus. Cytoplasmic staining should be ignored.

A second oestrogen receptor, ER-b, has been identified. The receptor detected by the previously available antibodies is now designated ER-a. A significant number of breast carcinomas are ER-a negative / ER-b positive: ER-b positivity correlates with prolonged survival on Tamoxifen, but large multivariate studies are needed⁴.

ERa consists of 595 amino acids organized in six functional regions¹⁹:

N-terminal

A/B transcription activation region C highly conserved DNA-binding domain, involved in dimerisation D hinge region; functions unknown E ligand-binding region, interacts with co-activators and co-repressors F functions unknown

C-terminal

ERb shows the greatest homology to ERa in the conserved DNA-binding domain.

ER-ligand binding has tissue-specific effects, including transcriptional activation or repression, regulation of other signalling pathways and effects on the cell cycle.

Immunohistochemical expression

• normal vulval and vaginal skin; epithelium and stromal cells¹

• vulval fibroepithelial polyps¹

• vulval smooth muscle tumours¹

• vulval nerve sheath tumours¹

• vulval and vaginal angiomyofibroblastoma¹

• breast carcinoma: the rate of expression increases with patient age and following the menopause¹⁹. Tamoxifen may reduce expression². Apocrine carcinomas of the breast are commonly positive for androgen receptors but negative for oestrogen receptors and progesterone receptors.

• epithelioid smooth muscle tumour

• melanoma

• meningioma

• sclerosing haemangioma

• desmoid tumour (abdominal fibromatosis)

• thyroid neoplasms

• thymomas

• carcinomas of steroid-dependent tissues:

  • ovary

  • endometrium

proliferative endometrium	96%3
secretory endometrium	42%3
hyperplastic endometrium	80%3
endometrial carcinoma	32%3

• cervix

• aggressive angiomyxoma of pelvic parts

• some lung carcinomas: the published literature is contradictory. Some early studies were biochemical examination of cytosol (4/21⁹, 6/15¹⁰, 3/19¹¹).

		ER	ER and PR
	Breast,	21/29 (using clone 6F-11, Novocastra Laboratories, Newcastle upon Tyne, England)5, 37/68 (using 6F11, 35/68 using 1D5, 29/68 using TE111)17, 52/107 (immunostaining histoscore >10)18	13/295
	Invasive ductal	81/129 (using clone 1D5)6
	Invasive lobular	6/106, 35/65 (using 6F11, 33/65 using 1D5, 27/65 using TE111)
	Ovary	19/225, 10/296, 16/24 (using either 1D5 or 6F11: 8/24 with TE111)17, 11/86 (immunostaining histoscore >10)18	10/225
	Endometrium	1/25	1/25
	Lung	0/33 (using clone 6F-11, Novocastra Laboratories, Newcastle upon Tyne, England)5, 0/35 (using clone 1D5)6, 3/42 (adenocarcinoma, using ER-ICA, Abbott Laboratories, North Chicago, Ill))7, 0/248 (non small cell carcinomas, using 1D5)8, 0/11112, 3/4913, 62/64 (details of pretreatment, antibody and dilution not given)15, 0/2316, 10/41 (using either 1D5 or 6F11: 0/41 with TE111)17	0/25, 0/248 (non small cell carcinomas)8, 1/4913
	Oesophagus	0/25	0/25
	Gallbladder	0/15	0/25
	Stomach	0/35, 0/396, 1/35 (using either 1D5 or 6F11: 0/35 with TE111)17	0/25
	Colon	0/256, 0/437, 0/22 (using either 1D5, 6F11 or TE111)17, 0/94 (immunostaining histoscore >10)18
	Pancreas	0/25, 0/266, 0/187, 0/22 (using either 1D5, 6F11 or TE111)17	0/25
	Kidney	0/456, 0/27 (using either 1D5, 6F11 or TE111)17
	Prostate	0/25	0/25

Using the tyramide signal amplification method, it is possible to increase sensitivity for steroid receptors. However, this results in an increased rate of staining in bronchogenic carcinomas; the small increase in sensitivity is more than outweighed by the loss of specificity, negating any benefit¹⁷.

The clone TE111 has a lower sensitivity than either 1D5 or 6F11, but has the advantage that it does not stain any tumours other than those of breast or ovary: in particular, bronchogenic carcinomas are reliably negative¹⁷.

Diagnostic utility

• Identification of adenocarcinoma as arising from breast or female genital tract, in combination with PR and various other markers.

• identification of those breast carcinomas which are likely to respond to hormone therapy.

• differentiation of endocervical from endometrial adenocarcinoma.

References

¹McCluggage WG, Patterson A, Axwell P. Aggressive angiomyxoma of pelvic parts exhibits oestrogen and progesterone receptor positivity. J Clin Pathol 2000;53:603-605.

²Verghese et al. Mitotic rate, ER and bcl-2 expression in short term Tamoxifen treated breast cancer. J Pathol 2001:193(suppl):31^A.

³Brican S et al. Expression of c-myc and c-jun in relation to estrogen receptor status in normal, hyperplastic and neoplastic endometrium. J Pathol 2001:193(suppl):3^4A.

⁴Mann, S., Laucirica, R., Carlson, N., Younes, P. S., Ali, N., Younes, A., Li, Y., Younes, M. Estrogen receptor beta expression in invasive breast cancer. Human Pathol 2001;32:113-118.

⁵Lee, B. H., J. L. Hecht, et al. (2002). "WT1, estrogen receptor, and progesterone receptor as markers for breast or ovarian primary sites in metastatic adenocarcinoma to body fluids." Am J Clin Pathol 117(5): 745-50. (using clone 6F-11, Novocastra Laboratories, Newcastle upon Tyne, England)

⁶Kaufmann, O., T. Deidesheimer, et al. (1996). "Immunohistochemical differentiation of metastatic breast carcinomas from metastatic adenocarcinomas of other common primary sites." Histopathology 29(3): 233-40. (using clone 1D5, Immunotech, Marseille, France)

⁷Ollayos, C. W., G. P. Riordan, et al. (1994). "Estrogen receptor detection in paraffin sections of adenocarcinoma of the colon, pancreas, and lung." Arch Pathol Lab Med 118(6): 630-2. (using ER-ICA, Abbott Laboratories, North Chicago, Ill))

⁸Di Nunno, L., L. G. Larsson, et al. (2000). "Estrogen and progesterone receptors in non-small cell lung cancer in 248 consecutive patients who underwent surgical resection." Arch Pathol Lab Med 124(10): 1467-70. (using 1D5)

⁹Chaudhuri PK, Thomas PA, Walker MJ, Briele HA, Das Gupta TK, Beattie CW. Steroid receptors in human lung cancer cytosols. Cancer Lett 1982;16:327–332.

¹⁰Beattie, C. W., N. W. Hansen, et al. (1985). "Steroid receptors in human lung cancer." Cancer Res 45(9): 4206-14.

¹¹Cagle, P. T., D. R. Mody, et al. (1990). "Estrogen and progesterone receptors in bronchogenic carcinoma." Cancer Res 50(20): 6632-5.

¹²Vargas SO. Leslie KO. Vacek PM. Socinski MA. Weaver DL. Estrogen- receptor- related protein p29 in primary nonsmall cell lung carcinoma: pathologic and prognostic correlations. Cancer 1998;82:1495-500.

¹³Su JM. Hsu HK. Chang H. Lin SL. Chang HC. Huang MS. Tseng HH. Expression of estrogen and progesterone receptors in non-small-cell lung cancer: immunohistochemical study. Anticancer Research 1996;16:3803-6.

¹⁵Canver, C. C., V. A. Memoli, et al. (1994). "Sex hormone receptors in non-small-cell lung cancer in human beings." J Thorac Cardiovasc Surg 108(1): 153-7.

¹⁶Brown, R. W., L. B. Campagna, et al. (1997). "Immunohistochemical identification of tumor markers in metastatic adenocarcinoma. A diagnostic adjunct in the determination of primary site." Am J Clin Pathol 107(1): 12-9.

¹⁷Kaufmann, O., S. Kother, et al. (1998). "Use of antibodies against estrogen and progesterone receptors to identify metastatic breast and ovarian carcinomas by conventional immunohistochemical and tyramide signal amplification methods." Mod Pathol 11(4): 357-63. (using 1D5 and 6F11, which give similar results)

¹⁸Lagendijk, J. H., H. Mullink, et al. (1999). "Immunohistochemical differentiation between primary adenocarcinomas of the ovary and ovarian metastases of colonic and breast origin. Comparison between a statistical and an intuitive approach." J Clin Pathol 52(4): 283-90.

¹⁹Diaz LK,Sneige N .Estrogen receptor analysis for breast cancer: current issues and keys to increasing testing accuracy. Adv Anat Pathol 2005; 12:10-9

This page last revised 23.3.2005.

©SMUHT/PW Bishop