Altered expression of E-cadherin in breast cancer: patterns, mechanisms and clinical significance

Reduced cell adhesion brought about by altered surface expression of E-cadh erin has been implicated in invasive and metastatic malignant growth. We in vestigated the patterns of immunohistochemical E-cadherin expression in 120 breast carcinomas. Furthermore. we analysed DNA from the same samples for loss of heterozygosity (LOH) using three separate microsatellite markers on chromosome 16q22.1. Finally, the clinical outcome was ascertained for 108 patients. 19% (18/97) of infiltrating ductal carcinomas showed complete los s of E-cadherin expression compared with 64% (9/14) of infiltrating lobular carcinomas. LOH was detected in 46% (24/52) of infiltrating ductal carcino mas and 89% (8/9) of infiltrating lobular carcinomas. In the infiltrating l obular carcinomas, LOH was associated with complete loss of cell membrane e xpression of E-cadherin, although a cytoplasmic expression pattern was evid ent. In contrast, this association was not seen in the infiltrating ductal carcinomas. In a multivariate analysis, loss of E-cadherin expression was s hown to be a significant independent risk factor for a poorer disease-free survival (P=0.019), ill particular in the node-negative subset of patients (P=0.029). Significance was also approached for breast cancer corrected sur vival (P=0.056). We conclude that different mechanisms are involved in the altered E-cadherin expression seen in different subtypes of breast carcinom as. Furthermore, we implicate loss of E-cadherin, regardless of the genetic causes, as an independent prognostic marker for disease recurrence, especi ally in node-negative breast cancer patients, irrespective of the histologi cal type. (C) 2000 Elsevier Science Ltd. All rights reserved.