Background: The expression of the homotypic cell adhesion protein, E-cadherin, is reduced in many types of cancer. The loss of this protein may be associated with metastasis because alteration of its function is required for invasion in vitro, and decreased expression has been associated with more aggressive tumor behavior in vivo. It is likely that the loss of downstream effector elements in the cadherin adhesion cascade may also disrupt cell-cell interactions and thereby promote invasion, but direct evidence for this has been lacking. One such effector element is alpha-catenin, a cytoplasmic protein related to vinculin that 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 immunocytochemistry 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 expression of E-cadherin (63% of cases). Cases with absent E-cadherin expression uniformly lacked alpha-catenin. Eight of the 26 patients (31%) had known metastatic disease at the time of biopsy; yet, all patients with normal alpha-catenin staining in their tumors were free of known metastatic disease (four patients).
Conclusions: Together with previous data on E-cadherin, these results suggest that reduced steady state levels of alpha-catenin may be a sensitive marker for disturbances in the adhesive function of the junctional complex and suggest that failure of at least one component of the cadherin-mediated cell-cell adhesion cascade is a common feature of breast, and presumably other, epithelial tumors.