Breast carcinomas that co-express E- and P-cadherin are associated with p120-catenin cytoplasmic localization and poor patient survival

Abstract

Changes in junctional catenin expression may compromise cadherin-mediated adhesion, increasing cell malignant properties such as invasive and metastatic abilities. In fact, altered expression of α-, β-, γ- and p120-catenin was reported as associated with E-cadherin loss or decreased expression, either in breast carcinomas or in breast cancer cell lines. We investigated the expression and subcellular localization of p120- and β-catenin in a series of human invasive breast carcinomas, and correlated it with biological markers and clinicopathological parameters. We demonstrated that both catenins frequently exhibit a reduced membranous or cytoplasmic staining pattern. These alterations were significantly correlated with lack of both E-cadherin and estrogen receptor-α expression. Considering β-catenin, it was also possible to associate its expression with histological grade, tumour size and nodal status, suggesting a relevant role for this catenin as a prognostic factor. Interestingly, we found that the majority of E- and P-cadherin co-expressing tumours were related with cytoplasmic expression of p120-catenin, being this group of breast carcinomas the one with poor patient survival. These results indicate that p120-catenin cytoplasmic accumulation may play an important role in mediating the oncogenic effects derived from P-cadherin aberrant expression, including enhanced motility and invasion, particularly in tumours which maintain E-cadherin expression.