Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1996 Oct;74(8):1237–1241. doi: 10.1038/bjc.1996.522

E-cadherin relates to EGFR expression and lymph node metastasis in primary breast carcinoma.

J L Jones 1, J E Royall 1, R A Walker 1
PMCID: PMC2075942  PMID: 8883410

Abstract

Expression of the calcium-dependent cell-cell adhesion molecule E-cadherin has been examined in 187 primary breast carcinomas using an immunohistochemical technique. The pattern and extent of reactivity has been correlated with clinicopathological data including tumour type, grade and lymph node status and with other prognostic parameters including oestrogen receptor (ER) status, expression of c-erbB-2, pS2 protein and epidermal growth factor receptor (EGFR). Two patterns of E-cadherin staining were observed in carcinomas, membrane reactivity and a diffuse cytoplasmic staining. A marked difference in expression of E-cadherin was observed between infiltrating lobular carcinomas (ILC) and infiltrating ductal carcinomas (IDC), the former showing complete loss of membrane staining, whereas 93% of IDC retained some level of expression. In IDC reactivity was not related to tumour grade but there was a significant association between reduced membrane levels of E-cadherin and the presence of lymph node metastasis, and a highly significant correlation between the presence of cytoplasmic E-cadherin and metastasis. A significant relationship was also demonstrated between reduced E-cadherin reactivity and expression of EGFR. These findings emphasise the complexity of control of E-cadherin in breast carcinomas and provide evidence of a link between membrane signalling pathways and modulation of E-cadherin expression.

Full text

PDF
1240

Images in this article

1238Figure 1
on p.1238
1239Figure 2
on p.1239
1239Figure 3
on p.1239
1239Figure 4
on p.1239

Selected References

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

  1. Becker K. F., Atkinson M. J., Reich U., Becker I., Nekarda H., Siewert J. R., Höfler H. E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. Cancer Res. 1994 Jul 15;54(14):3845–3852. [PubMed] [Google Scholar]
  2. Berger M. S., Locher G. W., Saurer S., Gullick W. J., Waterfield M. D., Groner B., Hynes N. E. Correlation of c-erbB-2 gene amplification and protein expression in human breast carcinoma with nodal status and nuclear grading. Cancer Res. 1988 Mar 1;48(5):1238–1243. [PubMed] [Google Scholar]
  3. Berx G., Cleton-Jansen A. M., Nollet F., de Leeuw W. J., van de Vijver M., Cornelisse C., van Roy F. E-cadherin is a tumour/invasion suppressor gene mutated in human lobular breast cancers. EMBO J. 1995 Dec 15;14(24):6107–6115. doi: 10.1002/j.1460-2075.1995.tb00301.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bracke M. E., Charlier C., Bruyneel E. A., Labit C., Mareel M. M., Castronovo V. Tamoxifen restores the E-cadherin function in human breast cancer MCF-7/6 cells and suppresses their invasive phenotype. Cancer Res. 1994 Sep 1;54(17):4607–4609. [PubMed] [Google Scholar]
  5. Coman D. R. Mechanism of the Invasiveness of Cancer. Science. 1947 Apr 4;105(2727):347–348. doi: 10.1126/science.105.2727.347. [DOI] [PubMed] [Google Scholar]
  6. D'souza B., Taylor-Papadimitriou J. Overexpression of ERBB2 in human mammary epithelial cells signals inhibition of transcription of the E-cadherin gene. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7202–7206. doi: 10.1073/pnas.91.15.7202. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Elston C. W., Ellis I. O. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991 Nov;19(5):403–410. doi: 10.1111/j.1365-2559.1991.tb00229.x. [DOI] [PubMed] [Google Scholar]
  8. Foekens J. A., Rio M. C., Seguin P., van Putten W. L., Fauque J., Nap M., Klijn J. G., Chambon P. Prediction of relapse and survival in breast cancer patients by pS2 protein status. Cancer Res. 1990 Jul 1;50(13):3832–3837. [PubMed] [Google Scholar]
  9. Frixen U. H., Behrens J., Sachs M., Eberle G., Voss B., Warda A., Löchner D., Birchmeier W. E-cadherin-mediated cell-cell adhesion prevents invasiveness of human carcinoma cells. J Cell Biol. 1991 Apr;113(1):173–185. doi: 10.1083/jcb.113.1.173. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hart I. R., Goode N. T., Wilson R. E. Molecular aspects of the metastatic cascade. Biochim Biophys Acta. 1989 Jul 28;989(1):65–84. doi: 10.1016/0304-419x(89)90035-8. [DOI] [PubMed] [Google Scholar]
  11. Hashimoto M., Niwa O., Nitta Y., Takeichi M., Yokoro K. Unstable expression of E-cadherin adhesion molecules in metastatic ovarian tumor cells. Jpn J Cancer Res. 1989 May;80(5):459–463. doi: 10.1111/j.1349-7006.1989.tb02336.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hinck L., Näthke I. S., Papkoff J., Nelson W. J. Dynamics of cadherin/catenin complex formation: novel protein interactions and pathways of complex assembly. J Cell Biol. 1994 Jun;125(6):1327–1340. doi: 10.1083/jcb.125.6.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hirano S., Kimoto N., Shimoyama Y., Hirohashi S., Takeichi M. Identification of a neural alpha-catenin as a key regulator of cadherin function and multicellular organization. Cell. 1992 Jul 24;70(2):293–301. doi: 10.1016/0092-8674(92)90103-j. [DOI] [PubMed] [Google Scholar]
  14. Hoschuetzky H., Aberle H., Kemler R. Beta-catenin mediates the interaction of the cadherin-catenin complex with epidermal growth factor receptor. J Cell Biol. 1994 Dec;127(5):1375–1380. doi: 10.1083/jcb.127.5.1375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hynes R. O. Integrins: versatility, modulation, and signaling in cell adhesion. Cell. 1992 Apr 3;69(1):11–25. doi: 10.1016/0092-8674(92)90115-s. [DOI] [PubMed] [Google Scholar]
  16. Kanai Y., Oda T., Tsuda H., Ochiai A., Hirohashi S. Point mutation of the E-cadherin gene in invasive lobular carcinoma of the breast. Jpn J Cancer Res. 1994 Oct;85(10):1035–1039. doi: 10.1111/j.1349-7006.1994.tb02902.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kemler R. Classical cadherins. Semin Cell Biol. 1992 Jun;3(3):149–155. doi: 10.1016/s1043-4682(10)80011-x. [DOI] [PubMed] [Google Scholar]
  18. Kemler R. From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet. 1993 Sep;9(9):317–321. doi: 10.1016/0168-9525(93)90250-l. [DOI] [PubMed] [Google Scholar]
  19. Kinsella A. R., Green B., Lepts G. C., Hill C. L., Bowie G., Taylor B. A. The role of the cell-cell adhesion molecule E-cadherin in large bowel tumour cell invasion and metastasis. Br J Cancer. 1993 May;67(5):904–909. doi: 10.1038/bjc.1993.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lipponen P., Saarelainen E., Ji H., Aaltomaa S., Syrjänen K. Expression of E-cadherin (E-CD) as related to other prognostic factors and survival in breast cancer. J Pathol. 1994 Oct;174(2):101–109. doi: 10.1002/path.1711740206. [DOI] [PubMed] [Google Scholar]
  21. Mareel M. M., Behrens J., Birchmeier W., De Bruyne G. K., Vleminckx K., Hoogewijs A., Fiers W. C., Van Roy F. M. Down-regulation of E-cadherin expression in Madin Darby canine kidney (MDCK) cells inside tumors of nude mice. Int J Cancer. 1991 Apr 1;47(6):922–928. doi: 10.1002/ijc.2910470623. [DOI] [PubMed] [Google Scholar]
  22. Mayer B., Johnson J. P., Leitl F., Jauch K. W., Heiss M. M., Schildberg F. W., Birchmeier W., Funke I. E-cadherin expression in primary and metastatic gastric cancer: down-regulation correlates with cellular dedifferentiation and glandular disintegration. Cancer Res. 1993 Apr 1;53(7):1690–1695. [PubMed] [Google Scholar]
  23. Moll R., Mitze M., Frixen U. H., Birchmeier W. Differential loss of E-cadherin expression in infiltrating ductal and lobular breast carcinomas. Am J Pathol. 1993 Dec;143(6):1731–1742. [PMC free article] [PubMed] [Google Scholar]
  24. Oka H., Shiozaki H., Kobayashi K., Inoue M., Tahara H., Kobayashi T., Takatsuka Y., Matsuyoshi N., Hirano S., Takeichi M. Expression of E-cadherin cell adhesion molecules in human breast cancer tissues and its relationship to metastasis. Cancer Res. 1993 Apr 1;53(7):1696–1701. [PubMed] [Google Scholar]
  25. Pignatelli M., Ansari T. W., Gunter P., Liu D., Hirano S., Takeichi M., Klöppel G., Lemoine N. R. Loss of membranous E-cadherin expression in pancreatic cancer: correlation with lymph node metastasis, high grade, and advanced stage. J Pathol. 1994 Dec;174(4):243–248. doi: 10.1002/path.1711740403. [DOI] [PubMed] [Google Scholar]
  26. 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]
  27. Schipper J. H., Frixen U. H., Behrens J., Unger A., Jahnke K., Birchmeier W. E-cadherin expression in squamous cell carcinomas of head and neck: inverse correlation with tumor dedifferentiation and lymph node metastasis. Cancer Res. 1991 Dec 1;51(23 Pt 1):6328–6337. [PubMed] [Google Scholar]
  28. Shiozaki H., Kadowaki T., Doki Y., Inoue M., Tamura S., Oka H., Iwazawa T., Matsui S., Shimaya K., Takeichi M. Effect of epidermal growth factor on cadherin-mediated adhesion in a human oesophageal cancer cell line. Br J Cancer. 1995 Feb;71(2):250–258. doi: 10.1038/bjc.1995.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Sommers C. L., Gelmann E. P., Kemler R., Cowin P., Byers S. W. Alterations in beta-catenin phosphorylation and plakoglobin expression in human breast cancer cells. Cancer Res. 1994 Jul 1;54(13):3544–3552. [PubMed] [Google Scholar]
  30. Springer T. A. Adhesion receptors of the immune system. Nature. 1990 Aug 2;346(6283):425–434. doi: 10.1038/346425a0. [DOI] [PubMed] [Google Scholar]
  31. Takeichi M. The cadherins: cell-cell adhesion molecules controlling animal morphogenesis. Development. 1988 Apr;102(4):639–655. doi: 10.1242/dev.102.4.639. [DOI] [PubMed] [Google Scholar]
  32. Vleminckx K., Vakaet L., Jr, Mareel M., Fiers W., van Roy F. Genetic manipulation of E-cadherin expression by epithelial tumor cells reveals an invasion suppressor role. Cell. 1991 Jul 12;66(1):107–119. doi: 10.1016/0092-8674(91)90143-m. [DOI] [PubMed] [Google Scholar]
  33. Walker R. A., Gullick W. J., Varley J. M. An evaluation of immunoreactivity for c-erbB-2 protein as a marker of poor short-term prognosis in breast cancer. Br J Cancer. 1989 Sep;60(3):426–429. doi: 10.1038/bjc.1989.299. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES