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Clinical Cancer Research Vol. 11, 5869-5877, August 15, 2005
© 2005 American Association for Cancer Research


Imaging, Diagnosis, Prognosis

P-Cadherin Overexpression Is an Indicator of Clinical Outcome in Invasive Breast Carcinomas and Is Associated with CDH3 Promoter Hypomethylation

Joana Paredes1, André Albergaria1, João T. Oliveira1, Carmen Jerónimo2,3, Fernanda Milanezi1,5 and Fernando C. Schmitt1,4

Authors' Affiliations: 1 Institute of Pathology and Molecular Immunology of Porto University (IPATIMUP); 2 Department of Genetics, Portuguese Oncology Institute of Porto; 3 School of Health Sciences - Fernando Pessoa University, Porto; 4 Medical Faculty, Porto University, Porto; and 5 School of Health Sciences, University of Minho, Braga, Portugal

Requests for reprints: Joana Paredes, Institute of Pathology and Molecular Immunology of Porto University, Rua Dr. Roberto Frias s/n 4200-465 Oporto, Portugal. Phone: 351-22557-0700; Fax: 351-22557-0799; E-mail: jparedes{at}ipatimup.pt.

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'-deoxycytidine 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.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
Cancer Prevention Journals Portal Cancer Reviews Online
Annual Meeting Education Book Meeting Abstracts Online
Copyright © 2005 by the American Association for Cancer Research.