P-cadherin overexpression is an indicator of clinical outcome in invasive breast carcinomas and is associated with CDH3 promoter hypomethylation

Abstract Purpose:P-cadherinoverexpressionhas been reported inbreast carcinomas, where it was asso-ciated with proliferative high-grade histological tumors. This study aimed to analyze P-cadherin expression in invasive breast cancer and to correlate it with tumor markers, pathologic features, and patient survival. Another purpose was to evaluate the P-cadherin promoter methylation pattern as themolecular mechanismunderlying this gene regulation. Experimental Design:Using a series of invasive breast carcinomas, P-cadherin expressionwas evaluated and correlated with histologic grade, estrogen receptor, MIB-1, and p53 and c-erbB-2 expression. In order to assess whether P-cadherin expression was associated with changes in CDH3 promoter methylation, we studied the methylation status of a gene 5V-flanking region in these same carcinomas.This analysis was also done for normal tissue and for a breast cancer cell line treatedwith a demethylating agent. Results:P-cadherinexpression showeda strongcorrelationwithhighhistologic grade, increased proliferation, c-erbB-2 and p53 expression, lack of estrogen receptor, and poor patient survival. This overexpressioncanbe regulatedbygenepromotermethylationbecause the5-Aza-2V-deoxy-cytidine treatment ofMCF-7/AZ cells increased P-cadherinmRNAandprotein levels. Additionally