Virchows Archiv A

, Volume 414, Issue 2, pp 157–164 | Cite as

Expression of epidermal growth factor receptor in benign and malignant primary tumours of the breast

  • P. Möller
  • G. Mechtersheimer
  • M. Kaufmann
  • G. Moldenhauer
  • F. Momburg
  • T. Mattfeldt
  • H. F. Otto
Article

Summary

Using the monoclonal antibody EGFR1, normal mammary gland and a series of 213 unselected primary breast tumours were investigated immunohistochemically for expression of epidermal growth factor receptor (EGFR). In normal breast EGFR was expressed in variable patterns in lobular, ductal, and myoepithelial cells. In fibroadenoma, EGFR was detectable in variable numbers of ductal and myoepithelial cells and in stromal fibroblasts. The myoepithelial compartment of 2 cystosarcomas phyllodes also expressed EGFR. Among the 197 carcinomas tested only 20.3% contained EGFR expressing tumour cells which represented a minority in 12.2%, the majority in 2.1%, and the entire neoplastic population in 6.1% of the cases. Again, non-neoplastic ductal remnants often contained EGFR positive myoepithelial and ductal cells whereas stromal fibro-blasts expressed EGFR only occasionally. We conclude that in contrast to the normal state, EGFR-expression is a rather rare phenomenon in breast carcinoma cells, positively correlated with a declining grade of differentiation (p<0.025) and at least occasionally associated with squamous metaplasia within the tumour, that EGFR expression is not exclusively restricted to cells of the epithelial lineage, and that EGFR may have other functions not related to proliferation, since it is commonly detectable in myoepithelial cells.

Key words

Epidermal growth factor receptor (EGFR) Breast carcinoma Fibroadenoma Myoepithelial cells Fibroblasts 

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References

  1. Bloom HJG, Richardson WW (1957) Histologic grading and prognosis in breast cancer. A study of 1409 cases of which 359 have been followed for 15 years. Br J Cancer 11:359–377Google Scholar
  2. Cattoretti A, Andreola S, Clemente C, D'Amato L, Rilke F (1988) Vimentin and p53 expression on epidermal growth factor receptor-positive, oestrogen receptor-negative breast carcinomas. Br J Cancer 57:353–357Google Scholar
  3. Fitzpatrick SL, Brightwell J, Wittliff JL, Barrows GH, Schultz GS (1984) Epidermal growth factor binding by breast tumor biopsies and relationship to estrogen receptor and progestin receptor levels. Cancer Res 44:3448–3453Google Scholar
  4. Glenney JR, Chen WS, Lazar CS, Walton GM, Zokas LM, Rosenfeld MG, Gill GN (1988) Ligand-induced endocytosis of the EGF receptor is blocked by mutational inactivation and by microinjection of antiphosphotyrosine antibodies. Cell 52:675–684Google Scholar
  5. Gusterson B, Cowley G, McIlhinney J, Ozanne B, Fisher C, Reeves B (1985) Evidence for increased epidermal growth factor receptors in human sarcomas. Int J Cancer 36:689–693Google Scholar
  6. Gusterson BA, Monaghan P, Mahendran R, Ellis J, O'Hare MJ (1986) Identification of myoepithelial cells in human and rat breasts by anti-common acute lymphoblastic leukemia antigen antibody A12. JNCI 77:343–349Google Scholar
  7. Hendler FJ, Ozanne BW (1984) Human squamous cell lung cancers express increased epidermal growth factor receptors. Am J Clin Invest 74:647–651Google Scholar
  8. Horne GM, Angus B, Wright C, Needham G, Nicholson S, Harris AL, Innes B, Horne CHW (1988) Relationships between oestrogen receptor, epidermal growth factor receptor, ER-D5, and P24 oestrogen regulated protein in human breast cancer. J Pathol 155:143–150Google Scholar
  9. Metzgar RS, Borowitz MJ, Jones NH, Dowell BL (1981) Distribution of common acute lymphoblastic leukemia antigen in nonhematopoietic tissues. J Exp Med 154:1249–1254Google Scholar
  10. Moldenhauer G, Momburg F, Möller P, Schwartz R, Hämmerling GJ (1987) Epithelium-specific surface glycoprotein of Mr 34,000 is a widely distributed human carcinoma marker. Br J Cancer 56:714–721Google Scholar
  11. Momburg F, Moldenhauer G, Hämmerling GJ, Möller P (1987) Immunohistochemical study of the expression of a Mr 34,000 human epithelium-specific surface glycoprotein in normal and malignant tissues. Cancer Res 47:2883–2891Google Scholar
  12. Moolenaar WH, Bierman AJ, Tilly BC, Verlaan I, Defize LHK, Honegger AM, Ullrich A, Schlessinger J (1988) A point mutation at the ATP-binding site of the EGF-receptor abolished signal transduction. EMBO J 7:707–710Google Scholar
  13. Pekonen F, Partanen S, Mäkinen T, Rutanen E-M (1988) Receptors for epidermal growth factor and insulin-like growth factor I and their relation to steroid receptors in human breast cancer. Cancer Res 48:1343–1347Google Scholar
  14. Pérez R, Pascual M, Macias A, Lage A (1984) Epidermal growth factor receptors in human breast cancer. Breast Cancer Res Treat 4:189–193Google Scholar
  15. Real FX, Rettig WJ, Chesa PG, Melamed MR, Old LJ, Mendelsohn J (1986) Expression of epidermal growth factor receptor in human cultured cells and tissues: Relationship to cell lineage and stage of differentiation. Cancer Res 46:4726–4731Google Scholar
  16. Ritz J, Pesando JM, Notis-McConarty J, Schlossman SF (1980) Modulation of human acute lymphoblastic leukemia antigen induced by monoclonal antibody in vitro. J Immunol 125:1506–1514Google Scholar
  17. Sainsbury JRC, Farndon JR, Sherbet VG, Harris AL (1985a) Epidermal-growth-factor receptors and oestrogen receptors in human breast cancer. Lancet i:364–366Google Scholar
  18. Sainsbury JRC, Malcolm AJ, Appleton DR, Farndon JR, Harris AL (1985b) Presence of epidermal growth factor receptor as an indicator of poor prognosis in patients with breast cancer. J Clin Pathol 38:1225–1228Google Scholar
  19. Sainsbury JRC, Farndon J, Needham GK, Malcolm AJ, Harris AL (1987) Epidermal-growth-factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet i:1398–1402Google Scholar
  20. Skoog L, Macias A, Azavedo E, Lombardero J, Klintenberg C (1986) Receptors for EGF and oestradiol and thymidinekinase activity in different histological subgroups of human mammary carcinomas. Br J Cancer 54:271–276Google Scholar
  21. Walker RA, Camplejohn RS (1986) DNA flow cytometry of human breast carcinomas and its relationship to transferrin and epidermal growth factor receptors. J Pathol 150:37–42Google Scholar
  22. Waterfield MD, Mayes ELV, Stroobant P, Bennet PLP, Young S, Goodfellow PN, Banting GS, Ozanne B (1982) A monoclonal antibody to the human epidermal growth factor receptor. J Cell Biochem 20:149–161Google Scholar
  23. Wrba F, Reiner A, Markis-Ritzinger E, Holzner JH (1988) Prognostic significance of immunohistochemical parameters in breast carcinomas. Path Res Pract 183:277–283Google Scholar
  24. Wright C, Angus B, Wetherall M, Udagawa Y, Sainsbury JRC, Johnston S, Carpenter F, Horne CHW (1987) Prognostic factors in breast cancer: immunohistochemical staining for SP1 and NCRC 11 related to survival, tumour epidermal growth factor receptor and oestrogen receptor status. J Pathol 153:325–331Google Scholar

Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • P. Möller
    • 1
  • G. Mechtersheimer
    • 1
  • M. Kaufmann
    • 2
  • G. Moldenhauer
    • 3
  • F. Momburg
    • 1
  • T. Mattfeldt
    • 1
  • H. F. Otto
    • 1
  1. 1.Pathologisches Institut der Universität HeidelbergHeidelbergGermany
  2. 2.Universitätsfrauenklinik HeidelbergHeidelbergGermany
  3. 3.Institut für Immunologie und Genetik am Deutschen KrebsforschungszentrumHeidelbergGermany

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