Reduced E-cadherin expression is associated with invasiveness and unfavorable prognosis in breast cancer

Am J Clin Pathol. 1996 Apr;105(4):394-402. doi: 10.1093/ajcp/105.4.394.


E-cadherin (E-cad) is a calcium-dependent, epithelial cell adhesion molecule whose reduced or lost expression has been associated with tumor dedifferentiation and increased metastatic potential in human carcinomas. The authors studied immunohistochemically E-cad expression in frozen sections of 362 breast carcinomas using a monoclonal antibody (HECD-1). The immunohistochemical detection of reduced E-cad expression was confirmed by mRNA in situ hybridization with two different oligonucleotide probes. THe proportion of tumors with reduced or lost E-cad expression increased significantly from pure intraductal carcinomas (20%, 4 of 20) through invasive ductal (IDCs; 52%, 124 of 239) to recurrent carcinomas (64%, 18 of 28; chi square test for trend, P = .004). Invasive lobular carcinomas (ILCs) and IDCs differed from each other in their E-cad expression. None of the ILCs (n=55) retained normal E-cad expression in contrast to 48% (115 of 239) of the IDCs. In 259 primary IDCs, reduced E-cad expression was associated with high histologic grade (chi square test for trend, P < .001), negative estrogen receptor status (ER; Fisher's exact test; P = .042), and marginally with axillary node involvement (Fisher's exact test, P = .063). In a subset of 109 primary IDC patients whose clinical follow-up was available (median follow-up 51 months), reduced E-cad expression was associated with shortened disease-free survival (DFS; Mantel-Cox test, P = .027). In Cox's multivariate regression analysis, progesterone receptor status (P = .018) and E-cad expression (P = .072) were selected as independent predictors of DFS. Our findings provide clinical evidence that loss of normal E-cad expression is an indicator of increased invasiveness and dedifferentiation in breast carcinoma. E-cad is a potentially important prognostic factor in primary IDCs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Cadherins / biosynthesis*
  • Carcinoma, Ductal, Breast / chemistry
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Intraductal, Noninfiltrating / chemistry
  • Carcinoma, Intraductal, Noninfiltrating / metabolism
  • Carcinoma, Intraductal, Noninfiltrating / pathology
  • Carcinoma, Lobular / chemistry
  • Carcinoma, Lobular / metabolism
  • Carcinoma, Lobular / pathology
  • Disease-Free Survival
  • Female
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Middle Aged
  • Neoplasm Invasiveness
  • Prognosis
  • RNA, Neoplasm / analysis
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis


  • Antibodies, Monoclonal
  • Cadherins
  • RNA, Neoplasm
  • Receptors, Estrogen
  • Receptors, Progesterone