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:

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

• • 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).

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

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

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

3 Brican 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):34A.

4 Mann, 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.

5 Lee, 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)

6 Kaufmann, 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)

7 Ollayos, 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))

8 Di 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)

9 Chaudhuri 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.

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

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

12 Vargas 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.

13 Su 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.

15 Canver, 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.

16 Brown, 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.

17 Kaufmann, 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)

18 Lagendijk, 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.

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

20 Lau SK, Chu PG,Weiss LM Immunohistochemical expression of estrogen receptor in pulmonary adenocarcinoma. Appl Immunohistochem Mol Morphol 2006; 14:83-7

21 Dennis JL, Hvidsten TR, Wit EC, et al. Markers of adenocarcinoma characteristic of the site of origin: development of a diagnostic algorithm. Clin Cancer Res 2005; 11:3766-72 FULL TEXT

22 Yang M, Nonaka D. A study of immunohistochemical differential expression in pulmonary and mammary carcinomas. Mod Pathol. 2010 May;23(5):654-61. (with corrections to the paper provided by author)

This page last revised 10.5.2010.

©SMUHT/PW Bishop