Simultaneous loss of E-cadherin and catenins in invasive lobular breast cancer and lobular carcinoma in situ

J Pathol. 1997 Dec;183(4):404-11. doi: 10.1002/(SICI)1096-9896(199712)183:4<404::AID-PATH1148>3.0.CO;2-9.


Loss of expression of the intercellular adhesion molecule E-cadherin frequently occurs in invasive lobular breast carcinomas as a result of mutational inactivation. Expression patterns of E-cadherin and the molecules comprising the cytoplasmic complex of adherens junctions, alpha-, beta- and gamma-catenin, were studied in a series of 38 lobular breast carcinomas with known E-cadherin mutation status. The effect of loss of E-cadherin by mutational inactivation (or other mechanisms) on the expression of catenins was investigated. Complete loss of plasma membrane-associated E-cadherin expression was observed in 32 out of 38 invasive lobular carcinomas, for which in 21 cases a mutation was found in the extracellular domain of E-cadherin. In total, 15 frameshift mutations of small deletions or insertions, ranging from 1 to 41 bp, three non-sense mutations, and three splice mutations were identified. Mutations were scattered over the whole coding region and no hot spots could be detected. In all cases, simultaneous loss of E-cadherin and alpha- and beta-catenin expression was found; in 50 per cent of these cases, additional loss of gamma-catenin was observed. In six invasive lobular carcinomas, expression of both E-cadherin and catenins was retained. In none of these carcinomas was an E-cadherin mutation detected. Lobular carcinoma in situ adjacent to invasive lobular carcinoma showed simultaneous loss of E-cadherin and catenins in all the cases studied--remarkably, also, in four cases positive for E-cadherin and catenin expression in the invasive component. These results indicate that simultaneous loss of E-cadherin and alpha-, beta- and gamma-catenin may be an important step in the formation of lobular carcinoma in situ, as a precursor of invasive lobular breast cancer. Events additional to E-cadherin inactivation must be involved in the transition of lobular carcinoma in situ to invasive lobular carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cadherins / genetics
  • Cadherins / metabolism*
  • Carcinoma in Situ / genetics
  • Carcinoma in Situ / metabolism
  • Carcinoma in Situ / pathology
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Ductal, Breast / metabolism*
  • Carcinoma, Ductal, Breast / pathology
  • Carcinoma, Lobular / genetics
  • Carcinoma, Lobular / metabolism*
  • Carcinoma, Lobular / pathology
  • Cytoskeletal Proteins / metabolism*
  • DNA Mutational Analysis
  • Desmoplakins
  • Female
  • Humans
  • Neoplasm Invasiveness
  • Trans-Activators*
  • alpha Catenin
  • beta Catenin
  • gamma Catenin


  • CTNNA1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • Cytoskeletal Proteins
  • Desmoplakins
  • JUP protein, human
  • Trans-Activators
  • alpha Catenin
  • beta Catenin
  • gamma Catenin