Journal of Cancer Research and Clinical Oncology

, Volume 131, Issue 1, pp 14–18

Expression of e-cadherin in high-risk breast cancer

  • Eugene M. Howard
  • Stephen K. Lau
  • Robert H. Lyles
  • George G. Birdsong
  • Jay N. Umbreit
  • Ruby Kochhar
Original Paper



E-cadherin expression is diverse, and differences in patient characteristics may produce variability in expression. Whereas some studies have indicated that downregulation of e-cadherin, associated with loss of cellular adhesiveness, was correlative with poor prognosis and metastasis, other studies have failed to confirm this. The present study uses a highly homogenous population of patients at high-risk for breast cancer, on the basis of ethnic and socio-economic status, to examine the relationship between e-cadherin and other prognostic markers in breast cancer.


Immunohistochemical staining was undertaken for estrogen (ER) and progesterone (PR) receptors, epidermal growth factor receptor 2 (Her-2), p53, vascular endothelial factor (VEGF), and hypoxia inducible factor 1α (HIF-1α) and the levels of these markers was compared to e-cadherin expression in a high-risk African-American patient population.


E-cadherin expression persisted into the later stagers of the disease, and was strongly associated with Her-2 and HIF-1α expression, but not p53, ER/PR or VEGF.


In contrast to other studies on heterogeneous populations, e-cadherin is preserved in aggressive tumors in this high-risk population. The ethnic and socio-economic risk stratification needs to be accounted for in studies correlating markers and prognosis.


Aggressive breast carcinoma E-cadherin HER-2 p53 VEGF HIF-1α Immunohistochemistry 



Human epidermal growth receptor 2


Vascular endothelial growth factor


Ductal carcinoma in situ


Hypoxia inducible factor 1α


Disease-free survival


Overall survival


  1. Adam L, Vadlamudi R, Kondapaka SB, Chernoff J, Mendelsohn J, Kumar R (1998) Hergulin regulates cytoskeletal reorganization and cell migration through the p21-activated kinase-1 via phosphatidylinositol-3 kinase. J Biol Chem 273:28238–28246CrossRefPubMedGoogle Scholar
  2. Asgeirsson KS, Jonasson JG, Tryggvaottir L, Olafsdottir K, Sigurgeirsdottir JR, Ingvarsson S, Ogmundsdottir HM (2000) Altered expression of e-cadherin in breast cancer: patterns, mechanisms and clinical significance. Eur J Cancer 36:1098–1106CrossRefPubMedGoogle Scholar
  3. Bankfalvi A, Terpe HJ, Breukelmann D, Bier B, Rempe D, Pschadka G, Krech R, Lelle RJ, Boecker W (1999) Immunophenotypic and prognostic analysis of E-cadherin and beta-catenin expression during breast carcinogenesis and tumour progression: a comparative study with CD44. Histopath 34:25–34CrossRefGoogle Scholar
  4. Bukholm IK, Nesland JM, Karensen R, Jacobsen U, Borresen-Dale AL (1997) Expression of e-cadherin and its relation to the p53 protein status in human breast carcinomas. Virchows Arch 431:317–321CrossRefPubMedGoogle Scholar
  5. Charpin C, Garcia S, Bouvier C, Devictor B, Andrac L, Choux R, Lavaut M (1997) E-cadherin quantitative immunocytochemical assays in breast carcinomas. J Pathol 181:294–300CrossRefPubMedGoogle Scholar
  6. Colpaert CG, Vermeulen PB, Benoy I, Soubry A, van Beest P, Goovaerts G, Dirix LY, Van Dam P, Fox SB, Harris AL, Van Maarck EA (2003) Inflammatory breast cancer shows angiogenesis with high endothelial proliferation rate and strong e-cadherin expression. Br J Cancer 88:718–725CrossRefPubMedGoogle Scholar
  7. D’Souza B, Taylor-Papdimitrou J (1994) Over-expression of ERBB2 in human mammary epithelial cells signals inhibition of transcription of the E-CD gene. Proc Natl Acad Sci 91:7202–7206PubMedGoogle Scholar
  8. Elzagheid A, Kuopio T, Ilmen M, Collan Y (2002) Prognostication of invasive ductal breast cancer by quantification of e-cadherin immunostaining: the methodology and clinical relevance. Histopath 41:127–133CrossRefGoogle Scholar
  9. Fearon ER (2003) Connecting estrogen receptor function, transcriptional repression, and e-cadherin expression in breast cancer. Cancer Cell 3:307–310CrossRefPubMedGoogle Scholar
  10. Gillett CE, Miles DW, Ryder K, Skilton D, Liebman RD, Springall RJ, Barnes DM, Hanby AM (2001) Retention of the expression of E-cadherin and catenins is associated with shorter survival in grade III ductal carcinoma of the breast. J Pathol 193:433–441CrossRefPubMedGoogle Scholar
  11. Heimann R, Lan F, McBride R, Hellman S (2000) Separating favorable from unfavorable prognostic markers in breast cancer: the role of e-cadherin. Cancer Res 60:298–304PubMedGoogle Scholar
  12. Jiang WG, Mansel RE (2000) E-cadherin complex and its abnormalities in human breast cancer. Surg Onc 9:151–171CrossRefGoogle Scholar
  13. Kemler R (1993) From cadherins to catenins: cytoplasmic protein interactions and regulation of cell adhesion. Trends Genet 9:317–321CrossRefPubMedGoogle Scholar
  14. Kleer CG, van Golen KL, Braun T, Merajver SD (2001) Persistent e-cadherin expression in inflammatory breast cancer. Modern Path 14:458–463CrossRefGoogle Scholar
  15. Kochhar R, Howard EM, Tadros TS, Birdsong GG, Lyles RH, Lau SK (2003) Correlation of p53, her2neu, vascular endothelial growth factor (VEGF) and e-cadherin expression in adenocarcinoma of breast. Proc AACR 6213Google Scholar
  16. Nakopoulou L, Gakiopoulou-Givalou H, Karayiannakis AJ, Giannopoulou I, Keramopoulos A, Davaris P, Pignatelli M (2002) Abnormal alpha-catenin expression in invasive breast cancer correlates with poor patient survival. Histopath 40:536–546CrossRefGoogle Scholar
  17. Palacios J, Benito N, Pizarro A, Limeres MA, Suarez A, Cano A, Gamallo C (1997) Relationship between ERBB2 and e-cadherin expression in human breast cancer. Virchows Arch 427:259–263Google Scholar
  18. Parker C, Rampaul RS, Pinder SE, Bell JA, Wencyk PM, Blamey RW, Nicholson RI, Robertson JF (2001) E-cadherin as a prognostic indicator in primary breast cancer. Br J Cancer 85:1958–1963CrossRefPubMedGoogle Scholar
  19. Rose DP, Royak-Schaler, R (2001) Tumor biology and prognosis in black breast cancer: a review. Cancer Det Prev 25:16–31Google Scholar
  20. Zhong H, Chiles K, Feldser D, Laughner E, Hanrahan C, Georgescu MM, Simons JW, Semenza GL (2000) Modulation of HIF-1α expression by the epidermal growth factor/phosphatidylinositol 3-kinase/PTEN/AKT/FRAP pathway in human prostate cancer cells: implications for tumor angiogenesis and therapeutics. Cancer Res 60:1541–1545PubMedGoogle Scholar
  21. Zschiesche W, Schonborn I, Behrens J, Herrenknecht K, Hartveit F, Lilleng P, Birchmeier W (1997) Expression of e-cadherin and catenins in invasive mammary carcinomas. Anticancer Res 17:561–567PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Eugene M. Howard
    • 1
  • Stephen K. Lau
    • 2
  • Robert H. Lyles
    • 3
  • George G. Birdsong
    • 2
  • Jay N. Umbreit
    • 1
  • Ruby Kochhar
    • 1
  1. 1.Winship Cancer InstituteEmory UniversityAtlantaUSA
  2. 2.Dept. of PathologyEmory University School of MedicineAtlantaUSA
  3. 3.Rollins School of Public Health at Emory UniversityAtlantaUSA

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