{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T01:56:36Z","timestamp":1775267796633,"version":"3.50.1"},"reference-count":43,"publisher":"American Association for Cancer Research (AACR)","issue":"16","content-domain":{"domain":["aacrjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2005,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>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.<\/jats:p>\n               <jats:p>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\u2032-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.<\/jats:p>\n               <jats:p>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\u2032-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.<\/jats:p>\n               <jats:p>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.<\/jats:p>","DOI":"10.1158\/1078-0432.ccr-05-0059","type":"journal-article","created":{"date-parts":[[2005,9,21]],"date-time":"2005-09-21T23:49:41Z","timestamp":1127346581000},"page":"5869-5877","update-policy":"https:\/\/doi.org\/10.1158\/crossmark_policy","source":"Crossref","is-referenced-by-count":211,"title":["P-Cadherin Overexpression Is an Indicator of Clinical Outcome in Invasive Breast Carcinomas and Is Associated with <i>CDH3<\/i> Promoter Hypomethylation"],"prefix":"10.1158","volume":"11","author":[{"given":"Joana","family":"Paredes","sequence":"first","affiliation":[{"name":"Authors' Affiliations: 1Institute of Pathology and Molecular Immunology of Porto University (IPATIMUP);"}]},{"given":"Andre\u0301","family":"Albergaria","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Institute of Pathology and Molecular Immunology of Porto University (IPATIMUP);"}]},{"given":"Joa\u0303o T.","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Institute of Pathology and Molecular Immunology of Porto University (IPATIMUP);"}]},{"given":"Carmen","family":"Jero\u0301nimo","sequence":"additional","affiliation":[{"name":"2Department of Genetics, Portuguese Oncology Institute of Porto;"},{"name":"3School of Health Sciences - Fernando Pessoa University, Porto;"}]},{"given":"Fernanda","family":"Milanezi","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Institute of Pathology and Molecular Immunology of Porto University (IPATIMUP);"},{"name":"5School of Health Sciences, University of Minho, Braga, Portugal"}]},{"given":"Fernando C.","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Authors' Affiliations: 1Institute of Pathology and Molecular Immunology of Porto University (IPATIMUP);"},{"name":"4Medical Faculty, Porto University, Porto; and"}]}],"member":"1086","published-online":{"date-parts":[[2005,8,22]]},"reference":[{"key":"2022061104074064500_B1","doi-asserted-by":"crossref","unstructured":"Conacci-Sorrell M, Zhurinsky J, Ben Ze'ev A. 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