P-cadherin expression in breast carcinoma indicates poor survival

BACKGROUND. The cadherin family of cell-cell adhesion molecules and their a ssociated proteins, the catenins, are essential to embryonic development an d the maintenance of adult tissues. During development, the homotypic inter action of a particular cadherin with an identical cadherin expressed on a n eighboring cell results in the sorting of cells to form distinctive tissues . Cadherins are believed to be tumor suppressors, and their altered express ion 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 br east 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 br east 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 estr ogen/progesterone receptor status. In ductal carcinomas, positive P-cadheri n expression correlated with a higher histologic grade. In con trast, expre ssion of E-cadherin was low in high grade ductal carcinomas but negative tu mors were uncommon. Negative or low E-cadherin expression did not correlate with poor survival. In lobular carcinomas, E-cadherin expression frequentl y was negative or low, and P-cadherin always was negative. CONCLUSIONS, Expression of P-cadherin in breast carcinoma is associated str ongly with poor survival and constitutes an independent prognostic predicto r. P-cad herin expression is a better indicator of clinical outcome than al terations in the expression of E-cadherin, N-cadherin, alpha-catenin, or be ta-catenin. Cancer 1999;86; 1263-72. (C) 1999 American Cancer Society.