Altered expression of E-cadherin in breast cancer patterns, mechanisms and clinical significance

2.50
Hdl Handle:
http://hdl.handle.net/2336/34816
Title:
Altered expression of E-cadherin in breast cancer patterns, mechanisms and clinical significance
Authors:
Asgeirsson, K S; Jonasson, J G; Tryggvadottir, L; Olafsdóttir, K; Sigurgeirsdottir, J R; Ingvarsson, S; Ogmundsdóttir, H M
Citation:
Eur. J. Cancer. 2000, 36(9):1098-106
Issue Date:
1-Jun-2000
Abstract:
Reduced cell adhesion brought about by altered surface expression of E-cadherin has been implicated in invasive and metastatic malignant growth. We investigated the patterns of immunohistochemical E-cadherin expression in 120 breast carcinomas. Furthermore, we analysed DNA from the same samples for loss of heterozygosity (LOH) using three separate microsatellite markers on chromosome 16q22.1. Finally, the clinical outcome was ascertained for 108 patients. 19% (18/97) of infiltrating ductal carcinomas showed complete loss of E-cadherin expression compared with 64% (9/14) of infiltrating lobular carcinomas. LOH was detected in 46% (24/52) of infiltrating ductal carcinomas and 89% (8/9) of infiltrating lobular carcinomas. In the infiltrating lobular carcinomas, LOH was associated with complete loss of cell membrane expression of E-cadherin, although a cytoplasmic expression pattern was evident. In contrast, this association was not seen in the infiltrating ductal carcinomas. In a multivariate analysis, loss of E-cadherin expression was shown to be a significant independent risk factor for a poorer disease-free survival (P=0.019), in particular in the node-negative subset of patients (P=0.029). Significance was also approached for breast cancer corrected survival (P=0.056). We conclude that different mechanisms are involved in the altered E-cadherin expression seen in different subtypes of breast carcinomas. Furthermore, we implicate loss of E-cadherin, regardless of the genetic causes, as an independent prognostic marker for disease recurrence, especially in node-negative breast cancer patients, irrespective of the histological type.
Description:
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field
Additional Links:
http://www.sciencedirect.com/science/article/B6T68-40GHP2Y-6/2/a38403fd2455a766dc69e1f7797b88fe

Full metadata record

DC FieldValue Language
dc.contributor.authorAsgeirsson, K S-
dc.contributor.authorJonasson, J G-
dc.contributor.authorTryggvadottir, L-
dc.contributor.authorOlafsdóttir, K-
dc.contributor.authorSigurgeirsdottir, J R-
dc.contributor.authorIngvarsson, S-
dc.contributor.authorOgmundsdóttir, H M-
dc.date.accessioned2008-08-08T11:41:22Z-
dc.date.available2008-08-08T11:41:22Z-
dc.date.issued2000-06-01-
dc.date.submitted2008-08-08-
dc.identifier.citationEur. J. Cancer. 2000, 36(9):1098-106en
dc.identifier.issn0959-8049-
dc.identifier.pmid10854942-
dc.identifier.doi10.1016/S0959-8049(00)00062-9-
dc.identifier.urihttp://hdl.handle.net/2336/34816-
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractReduced cell adhesion brought about by altered surface expression of E-cadherin has been implicated in invasive and metastatic malignant growth. We investigated the patterns of immunohistochemical E-cadherin expression in 120 breast carcinomas. Furthermore, we analysed DNA from the same samples for loss of heterozygosity (LOH) using three separate microsatellite markers on chromosome 16q22.1. Finally, the clinical outcome was ascertained for 108 patients. 19% (18/97) of infiltrating ductal carcinomas showed complete loss of E-cadherin expression compared with 64% (9/14) of infiltrating lobular carcinomas. LOH was detected in 46% (24/52) of infiltrating ductal carcinomas and 89% (8/9) of infiltrating lobular carcinomas. In the infiltrating lobular carcinomas, LOH was associated with complete loss of cell membrane expression of E-cadherin, although a cytoplasmic expression pattern was evident. In contrast, this association was not seen in the infiltrating ductal carcinomas. In a multivariate analysis, loss of E-cadherin expression was shown to be a significant independent risk factor for a poorer disease-free survival (P=0.019), in particular in the node-negative subset of patients (P=0.029). Significance was also approached for breast cancer corrected survival (P=0.056). We conclude that different mechanisms are involved in the altered E-cadherin expression seen in different subtypes of breast carcinomas. Furthermore, we implicate loss of E-cadherin, regardless of the genetic causes, as an independent prognostic marker for disease recurrence, especially in node-negative breast cancer patients, irrespective of the histological type.en
dc.language.isoenen
dc.publisherElsevier Science Ltden
dc.relation.urlhttp://www.sciencedirect.com/science/article/B6T68-40GHP2Y-6/2/a38403fd2455a766dc69e1f7797b88feen
dc.subject.meshAdulten
dc.subject.meshAgeden
dc.subject.meshAged, 80 and overen
dc.subject.meshBreast Neoplasmsen
dc.subject.meshCadherinsen
dc.subject.meshDNA, Neoplasmen
dc.subject.meshDisease-Free Survivalen
dc.subject.meshFemaleen
dc.subject.meshHumansen
dc.subject.meshImmunohistochemistryen
dc.subject.meshLoss of Heterozygosityen
dc.subject.meshMicrosatellite Repeatsen
dc.subject.meshMiddle Ageden
dc.subject.meshMutationen
dc.subject.meshNeoplasm Metastasisen
dc.subject.meshNeoplasm Proteinsen
dc.subject.meshNeoplasm Recurrence, Localen
dc.subject.meshPolymerase Chain Reactionen
dc.subject.meshPrognosisen
dc.titleAltered expression of E-cadherin in breast cancer patterns, mechanisms and clinical significanceen
dc.typeArticleen
dc.contributor.departmentMolecular and Cell Biology Laboratory, Icelandic Cancer Society, PO Box 5420, Reykjavík, Iceland.en
dc.identifier.journalEuropean journal of cancer (Oxford, England : 1990)en

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