Skip to main content
PMC home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1994 Jun;144(6):1238–1246.

Differential expression of estrogen, progesterone, and epidermal growth factor receptors in normal, benign, and malignant human breast tissues using dual staining immunohistochemistry.

T van Agthoven 1, M Timmermans 1, J A Foekens 1, L C Dorssers 1, S C Henzen-Logmans 1
PMCID: PMC1887470  PMID: 7515559

Abstract

Distribution of estrogen (ER), progesterone (PR) receptors, and epidermal growth factor (EGF) receptors was assayed by dual staining immunohistochemistry on 28 selected cytosolic ER-positive breast carcinomas and 22 nonmalignant breast tissues. ER-positive tumor cells were detected in 26 (93%) and EGF receptor positive tumor cells were detected in 7 (25%) carcinomas. In five tumors both ER and EGF receptors were detected but localized in distinct tumor cells. Only in one case of ductal carcinoma in situ co-expression was observed in a subset of tumor cells. In contrast, simultaneous expression of ER/PR and EGF receptors was observed in non-neoplastic ductal remnants in the majority of the carcinomas and the fibroadenomas. In addition, double-positive cells were occasionally detected in luminal epithelial cells of normal breast tissue and mastopathies. This study shows that ER/PR and EGF receptors in breast tumor cells are inversely related at the single cell level. However, demonstration of ER/PR and EGF receptors in individual normal luminal cells shows that expression is not mutually exclusive.

Full text

PDF
1238

Images in this article

1241Figure 1
on p.1241
1243Figure 2
on p.1243

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barker S., Panahy C., Puddefoot J. R., Goode A. W., Vinson G. P. Epidermal growth factor receptor and oestrogen receptors in the non-malignant part of the cancerous breast. Br J Cancer. 1989 Nov;60(5):673–677. doi: 10.1038/bjc.1989.338. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beato M. Gene regulation by steroid hormones. Cell. 1989 Feb 10;56(3):335–344. doi: 10.1016/0092-8674(89)90237-7. [DOI] [PubMed] [Google Scholar]
  3. Benraad T. J., Foekens J. A. Hydroxyapatite assay to measure epidermal growth factor receptor in human primary breast tumors. Ann Clin Biochem. 1990 May;27(Pt 3):272–273. doi: 10.1177/000456329002700316. [DOI] [PubMed] [Google Scholar]
  4. DeSombre E. R., Carbone P. P., Jensen E. V., McGuire W. L., Wells S. A., Jr, Wittliff J. L., Lipsett M. B. Special report. Steriod receptors in breast cancer. N Engl J Med. 1979 Nov 1;301(18):1011–1012. doi: 10.1056/NEJM197911013011826. [DOI] [PubMed] [Google Scholar]
  5. Defize L. H., Mummery C. L., Moolenaar W. H., de Laat S. W. Antireceptor antibodies in the study of EGF-receptor interaction. Cell Differ. 1987 Mar;20(2-3):87–102. doi: 10.1016/0045-6039(87)90423-4. [DOI] [PubMed] [Google Scholar]
  6. Dorssers L. C., van Agthoven T., Dekker A., van Agthoven T. L., Kok E. M. Induction of antiestrogen resistance in human breast cancer cells by random insertional mutagenesis using defective retroviruses: identification of bcar-1, a common integration site. Mol Endocrinol. 1993 Jul;7(7):870–878. doi: 10.1210/mend.7.7.8413311. [DOI] [PubMed] [Google Scholar]
  7. Evans R. M. The steroid and thyroid hormone receptor superfamily. Science. 1988 May 13;240(4854):889–895. doi: 10.1126/science.3283939. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fisher B., Redmond C., Brown A., Wickerham D. L., Wolmark N., Allegra J., Escher G., Lippman M., Savlov E., Wittliff J. Influence of tumor estrogen and progesterone receptor levels on the response to tamoxifen and chemotherapy in primary breast cancer. J Clin Oncol. 1983 Apr;1(4):227–241. doi: 10.1200/JCO.1983.1.4.227. [DOI] [PubMed] [Google Scholar]
  9. Fuqua S. A., Fitzgerald S. D., Chamness G. C., Tandon A. K., McDonnell D. P., Nawaz Z., O'Malley B. W., McGuire W. L. Variant human breast tumor estrogen receptor with constitutive transcriptional activity. Cancer Res. 1991 Jan 1;51(1):105–109. [PubMed] [Google Scholar]
  10. Gerdin E., Juhlin C., Malmgren M., Gerdin B. Immunohistochemical identification of receptors for epidermal growth factor in tumor endothelium may be affected by cross-reactivity to blood group A antigen. Am J Clin Pathol. 1993 Jan;99(1):28–31. doi: 10.1093/ajcp/99.1.28. [DOI] [PubMed] [Google Scholar]
  11. Greene G. L., Sobel N. B., King W. J., Jensen E. V. Immunochemical studies of estrogen receptors. J Steroid Biochem. 1984 Jan;20(1):51–56. doi: 10.1016/0022-4731(84)90188-2. [DOI] [PubMed] [Google Scholar]
  12. Horwitz K. B., McGuire W. L. Estrogen control of progesterone receptor in human breast cancer. Correlation with nuclear processing of estrogen receptor. J Biol Chem. 1978 Apr 10;253(7):2223–2228. [PubMed] [Google Scholar]
  13. Horwitz K. B. Mechanisms of hormone resistance in breast cancer. Breast Cancer Res Treat. 1993;26(2):119–130. doi: 10.1007/BF00689685. [DOI] [PubMed] [Google Scholar]
  14. Jensen E. V. Hormone dependency of breast cancer. Cancer. 1981 May 15;47(10):2319–2326. doi: 10.1002/1097-0142(19810515)47:10<2319::aid-cncr2820471002>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  15. Jiang S. Y., Jordan V. C. Growth regulation of estrogen receptor-negative breast cancer cells transfected with complementary DNAs for estrogen receptor. J Natl Cancer Inst. 1992 Apr 15;84(8):580–591. doi: 10.1093/jnci/84.8.580. [DOI] [PubMed] [Google Scholar]
  16. King R. J. William L. McGuire Memorial Symposium. Estrogen and progestin effects in human breast carcinogenesis. Breast Cancer Res Treat. 1993;27(1-2):3–15. doi: 10.1007/BF00683189. [DOI] [PubMed] [Google Scholar]
  17. Klijn J. G., Berns P. M., Schmitz P. I., Foekens J. A. The clinical significance of epidermal growth factor receptor (EGF-R) in human breast cancer: a review on 5232 patients. Endocr Rev. 1992 Feb;13(1):3–17. doi: 10.1210/edrv-13-1-3. [DOI] [PubMed] [Google Scholar]
  18. Koenders P. G., Beex L. V., Geurts-Moespot A., Heuvel J. J., Kienhuis C. B., Benraad T. J. Epidermal growth factor receptor-negative tumors are predominantly confined to the subgroup of estradiol receptor-positive human primary breast cancers. Cancer Res. 1991 Sep 1;51(17):4544–4548. [PubMed] [Google Scholar]
  19. McGuire W. L., Chamness G. C., Fuqua S. A. Estrogen receptor variants in clinical breast cancer. Mol Endocrinol. 1991 Nov;5(11):1571–1577. doi: 10.1210/mend-5-11-1571. [DOI] [PubMed] [Google Scholar]
  20. McGuire W. L., Clark G. M., Dressler L. G., Owens M. A. Role of steroid hormone receptors as prognostic factors in primary breast cancer. NCI Monogr. 1986;(1):19–23. [PubMed] [Google Scholar]
  21. McGuire W. L. Prognostic factors for recurrence and survival in human breast cancer. Breast Cancer Res Treat. 1987 Oct;10(1):5–9. doi: 10.1007/BF01806129. [DOI] [PubMed] [Google Scholar]
  22. Miller A. D., Rosman G. J. Improved retroviral vectors for gene transfer and expression. Biotechniques. 1989 Oct;7(9):980-2, 984-6, 989-90. [PMC free article] [PubMed] [Google Scholar]
  23. Nicholson S., Sainsbury J. R., Halcrow P., Chambers P., Farndon J. R., Harris A. L. Expression of epidermal growth factor receptors associated with lack of response to endocrine therapy in recurrent breast cancer. Lancet. 1989 Jan 28;1(8631):182–185. doi: 10.1016/s0140-6736(89)91202-6. [DOI] [PubMed] [Google Scholar]
  24. Parl F. F., Posey Y. F. Discrepancies of the biochemical and immunohistochemical estrogen receptor assays in breast cancer. Hum Pathol. 1988 Aug;19(8):960–966. doi: 10.1016/s0046-8177(88)80013-3. [DOI] [PubMed] [Google Scholar]
  25. Read L. D., Keith D., Jr, Slamon D. J., Katzenellenbogen B. S. Hormonal modulation of HER-2/neu protooncogene messenger ribonucleic acid and p185 protein expression in human breast cancer cell lines. Cancer Res. 1990 Jul 1;50(13):3947–3951. [PubMed] [Google Scholar]
  26. Robertson J. F., Bates K., Pearson D., Blamey R. W., Nicholson R. I. Comparison of two oestrogen receptor assays in the prediction of the clinical course of patients with advanced breast cancer. Br J Cancer. 1992 May;65(5):727–730. doi: 10.1038/bjc.1992.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Russell K. S., Hung M. C. Transcriptional repression of the neu protooncogene by estrogen stimulated estrogen receptor. Cancer Res. 1992 Dec 1;52(23):6624–6629. [PubMed] [Google Scholar]
  28. Sainsbury J. R., Farndon J. R., Needham G. K., Malcolm A. J., Harris A. L. Epidermal-growth-factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet. 1987 Jun 20;1(8547):1398–1402. doi: 10.1016/s0140-6736(87)90593-9. [DOI] [PubMed] [Google Scholar]
  29. Toi M., Hamada Y., Nakamura T., Mukaida H., Suehiro S., Wada T., Toge T., Niimoto M., Hattori T. Immunocytochemical and biochemical analysis of epidermal growth factor receptor expression in human breast cancer tissues: relationship to estrogen receptor and lymphatic invasion. Int J Cancer. 1989 Feb 15;43(2):220–225. doi: 10.1002/ijc.2910430208. [DOI] [PubMed] [Google Scholar]
  30. Tora L., Mullick A., Metzger D., Ponglikitmongkol M., Park I., Chambon P. The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties. EMBO J. 1989 Jul;8(7):1981–1986. doi: 10.1002/j.1460-2075.1989.tb03604.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Ullrich A., Coussens L., Hayflick J. S., Dull T. J., Gray A., Tam A. W., Lee J., Yarden Y., Libermann T. A., Schlessinger J. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. 1984 May 31-Jun 6Nature. 309(5967):418–425. doi: 10.1038/309418a0. [DOI] [PubMed] [Google Scholar]
  32. Wärri A. M., Laine A. M., Majasuo K. E., Alitalo K. K., Härkönen P. L. Estrogen suppression of erbB2 expression is associated with increased growth rate of ZR-75-1 human breast cancer cells in vitro and in nude mice. Int J Cancer. 1991 Oct 21;49(4):616–623. doi: 10.1002/ijc.2910490425. [DOI] [PubMed] [Google Scholar]
  33. van Agthoven T., van Agthoven T. L., Portengen H., Foekens J. A., Dorssers L. C. Ectopic expression of epidermal growth factor receptors induces hormone independence in ZR-75-1 human breast cancer cells. Cancer Res. 1992 Sep 15;52(18):5082–5088. [PubMed] [Google Scholar]
  34. von Rüden T., Wagner E. F. Expression of functional human EGF receptor on murine bone marrow cells. EMBO J. 1988 Sep;7(9):2749–2756. doi: 10.1002/j.1460-2075.1988.tb03129.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES