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TitleP-cadherin overexpression Is an indicator of clinical outcome in invasive breast carcinomas and is associated with CDH3 promoter hypomethylation
Author(s)Paredes, Joana
Albergaria, André
Oliveira, João T.
Jerónimo, Carmen
Milanezi, Fernanda
Schmitt, Fernando C.
Issue dateAug-2005
PublisherAmerican Association for Cancer Research
JournalClinical cancer research
Citation"Clinical cancer research". ISSN 1078-0432. 11:16 (Aug. 2005) 186-5877.
Abstract(s)Purpose: P-cadherin overexpressionhas been reported in breast carcinomas,where itwas associated 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 the molecularmechanismunderlying 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 strong correlationwithhighhistologic grade, increased proliferation, c-erbB-2 and p53 expression, lack of estrogen receptor, and poor patient survival. This overexpressioncanbe regulatedby gene promotermethylationbecause the 5-Aza-2V-deoxycytidine treatment ofMCF-7/AZ cells increased P-cadherinmRNA and proteinlevels. Additionally, we found that 71% of P- adherin-negative cases showed promoter methylation,whereas 65% of positive ones were unmethylated (P = 0.005). The normal P-cadherin-negative breast epithelial cells showed consistent CDH3 promotermethylation. Conclusions: P-cadherin expressionwas strongly associatedwith tumor aggressiveness, being a good indicator of clinical outcome. Moreover, the aberrant expression of P-cadherin in breast cancermight be regulated by gene promoter hypomethylation.
AccessOpen access
Appears in Collections:3B’s - Artigos em revistas/Papers in scientific journals
ICVS - Artigos em Revistas Internacionais com Referee

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