P-cadherin expression in breast carcinoma indicates poor survival

BACKGROUND: The cadherin family of cell-cell adhesion molecules and their associated proteins, the catenins, are essential to embryonic development and the maintenance of adult tissues. During development, the homotypic interaction of a particular cadherin with an identical cadherin expressed on a neighboring cell results in the sorting of cells to form distinctive tissues. Cadherins are believed to be tumor suppressors, and their altered expression and function have been associated with tumor development. METHODS: The authors examined the expression of P-cadherin, E-cadherin, and N-cadherin, and alpha-catenin and beta-catenin in 183 cases of invasive breast carcinoma by immunohistochemistry on paraffin sections using specific antibodies and a steam-based antigen retrieval method. RESULTS: P-cadherin was positive in 95 cases and negative in 88 cases of breast carcinoma. Positive P-cadherin expression in breast carcinoma showed a strong correlation with poor patient prognosis. Five years after surgery, 90% of the patients with P-cadherin negative tumors were alive in contrast to only 59% of patients with P-cadherin positive tumors. The difference in survival reached statistical significance (P = 0.0001) as early as 2 years after surgical treatment. Expression of N-cadherin, alpha-catenin, and beta-catenin did not correlate with patient survival. Multivariable statistical analyses of the data showed that expression of P-cadherin was independent of tumor size and lymph node metastases, but correlated inversely with estrogen/progesterone receptor status. In ductal carcinomas, positive P-cadherin expression correlated with a higher histologic grade. In contrast, expression of E-cadherin was low in high grade ductal carcinomas but negative tumors were uncommon. Negative or low E-cadherin expression did not correlate with poor survival. In lobular carcinomas, E-cadherin expression frequently was negative or low, and P-cadherin always was negative. CONCLUSIONS: Expression of P-cadherin in breast carcinoma is associated strongly with poor survival and constitutes an independent prognostic predictor. P-cadherin expression is a better indicator of clinical outcome than alterations in the expression of E-cadherin, N-cadherin, alpha-catenin, or beta-catenin.