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

• Type: Article in International Scientific Journal
• Date: 2005

Authors

Joana Paredes (Author) Other; Albergaria, A (Author) Other; Oliveira, MJ (Author) Other; Carmen Jeronimo (Author) Other; Milanezi, F (Author) Other; Fernando Schmitt (Author) FMUP

Journal

Title: Clinical Cancer Research

Vol. 11

Pages: 5869-5877

ISSN: 1078-0432

Publisher: American Association for Cancer Research

Indexing

ISI Web of Knowledge - 195 Citations

Scopus - 214 Citations

Other information

Authenticus ID: P-000-1XG

DOI: 10.1158/1078-0432.ccr-05-0059

Abstract (EN): Purpose: P-cadherin overexpression has been reported in breast carcinomas, where it was 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 molecular mechanism underlying this gene regulation. Experimental Design: Using a series of invasive breast carcinomas, P-cadherin expression was 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 5'-flanking region in these same carcinomas. This analysis was also done for normal tissue and for a breast cancer cell line treated with a demethylating agent. Results: P-cadherin expression showed a strong correlation with high histologic grade, increased proliferation, c-erbB-2 and p53 expression, lack of estrogen receptor, and poor patient survival. This overexpression can be regulated by gene promoter methylation because the 5-Aza-2'-deoxy-cytidine treatment of MCF-7/AZ cells increased P-cadherin mRNA and protein levels. Additionally, we found that 71% of P-cadherin-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 promoter methylation. Conclusions: P-cadherin expression was strongly associated with tumor aggressiveness, being a good indicator of clinical outcome. Moreover, the aberrant expression of P-cadherin in breast cancer might be regulated by gene promoter hypomethylation.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 9