REDUCED ALPHA-CATENIN AND E-CADHERIN EXPRESSION IN BREAST-CANCER

BACKGROUND: The expression of the homotypic cell adhesion protein, E-c adherin, is reduced in many types of cancer. The loss of this protein may be associated with metastasis because alteration of its function i s required for invasion in vitro, and decreased expression has been as sociated with more aggressive tumor behavior in vivo. It is likely tha t the loss of downstream effector elements in the cadherin adhesion ca scade may also disrupt cell-cell interactions and thereby promote inva sion, but direct evidence for this has been lacking. One such effector element is alpha-catenin, a cytoplasmic protein related to vinculin t hat is associated in vivo with E-cadherin. EXPERIMENTAL DESIGN: In the present study, antibodies prepared to recombinant human alpha-catenin and recombinant human E-cadherin have been used to explore by immunoc ytochemistry the steady state levels of these proteins in a series of 26 cancers of the breast. RESULTS: The expression of alpha-catenin was reduced or lost more frequently (81% of cases) than was the expressio n of E-cadherin (63% of cases). Cases with absent E-cadherin expressio n uniformly lacked alpha-catenin. Eight of the 26 patients (31%) had k nown metastatic disease at the time of biopsy; yet, all patients with normal alpha-catenin staining in their tumors were free of known metas tatic disease (four patients). CONCLUSIONS: Together with previous dat a on E-cadherin, these results suggest that reduced steady state level s of alpha-catenin may be a sensitive marker for disturbances in the a dhesive function of the junctional complex and suggest that failure of at least one component of the cadherin-mediated cell-cell adhesion ca scade is a common feature of breast, and presumably other, epithelial tumors.