REDUCED E-CADHERIN EXPRESSION IS ASSOCIATED WITH INVASIVENESS AND UNFAVORABLE PROGNOSIS IN BREAST-CANCER

E-cadherin (E-cad) is a calcium-dependent, epithelial cell adhesion mo lecule whose reduced or lost expression has been associated with tumor dedifferentiation and increased metastatic potential in human carcino mas, The authors studied immunohistochemically E-cad expression in fro zen sections of 362 breast carcinomas using a monoclonal antibody (HEC D-1). The immunohistochemical detection of reduced Ecad expression was confirmed by mRNA in situ hybridization with two different oligonucle otide probes. The proportion of tumors with reduced or lost E-cad expr ession 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). Invas ive lobular carcinomas (ILCs) and IDCs differed from each other in the ir E-cad expression. None of the ILCs (n = 55) retained normal E-cad e xpression in contrast to 48% (115 of 239) of the IDCs. In 259 primary IDCs, reduced E-cad expression was associated with high histologic gra de (chi square test for trend, P < .001), negative estrogen receptor s tatus (ER; Fisher's exact test, P = .042), and marginally with axillar y node involvement (Fisher's exact test, P = .063), In a subset of 109 primary IDC patients whose clinical follow-up was available (median f ollow-up 51 months), reduced E-cad expression was associated with shor tened 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 pred ictors of DFS. Our findings provide clinical evidence that loss of nor mal E-cad expression is an indicator of increased invasiveness and ded ifferentiation in breast carcinoma. E-cad is a potentially important p rognostic factor in primary IDCs.