Source:http://linkedlifedata.com/resource/pubmed/id/18379416
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
5
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pubmed:dateCreated |
2008-4-28
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pubmed:abstractText |
Invasive lobular carcinoma (ILC) and lobular carcinoma in situ characteristically show loss of E-cadherin expression and so immunohistochemistry for E-cadherin is being increasingly used as a tool to differentiate between lobular and ductal lesions in challenging situations. However, misinterpretation of "aberrant" positive staining may lead some to exclude a diagnosis of lobular carcinoma. E-cadherin and beta-catenin immunohistochemistry was analyzed in 25 ILCs. E-cadherin "positive" ILCs were subjected to molecular analysis including comparative genomic hybridization. Different morphologic components of case 25, showing heterogenous E-cadherin expression, were analyzed by E-cadherin gene sequencing, methylation, and DASL gene expression profiling. Four ILCs were positive for E-cadherin, but each also had neoplastic cells with aberrant staining. Two of these ILCs were positive for beta-catenin, again with some aberrantly stained neoplastic cells, and 2 were negative. The solid component of case 25 was positive for E-cadherin whereas the classic and alveolar areas were negative. All components harbored an in-frame deletion in exon 7 (867del24) of the E-cadherin gene and loss of the wild type allele. Comparative genomic hybridization demonstrated evidence of clonal evolution from E-cadherin-positive to E-cadherin-negative components. E-cadherin down-regulation seems to be through transcriptional repression via activation of transforming growth factor-beta/SMAD2 rather than methylation. Positive staining for E-cadherin should not preclude a diagnosis of lobular in favor of ductal carcinoma. Molecular evidence suggests that even when E-cadherin is expressed, the cadherin-catenin complex maybe nonfunctional. Misclassification of tumors may lead to mismanagement of patients in clinical practice, particularly in the context of in situ disease at margins.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cadherins,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Neoplasm,
http://linkedlifedata.com/resource/pubmed/chemical/SMAD2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Smad2 Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Markers, Biological
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1532-0979
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
773-83
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pubmed:meshHeading |
pubmed-meshheading:18379416-Breast Neoplasms,
pubmed-meshheading:18379416-Cadherins,
pubmed-meshheading:18379416-Carcinoma, Ductal,
pubmed-meshheading:18379416-Carcinoma, Intraductal, Noninfiltrating,
pubmed-meshheading:18379416-Carcinoma, Lobular,
pubmed-meshheading:18379416-Carcinoma in Situ,
pubmed-meshheading:18379416-DNA, Neoplasm,
pubmed-meshheading:18379416-DNA Methylation,
pubmed-meshheading:18379416-Diagnosis, Differential,
pubmed-meshheading:18379416-Female,
pubmed-meshheading:18379416-Gene Expression Profiling,
pubmed-meshheading:18379416-Humans,
pubmed-meshheading:18379416-Immunohistochemistry,
pubmed-meshheading:18379416-Loss of Heterozygosity,
pubmed-meshheading:18379416-Nucleic Acid Hybridization,
pubmed-meshheading:18379416-Oligonucleotide Array Sequence Analysis,
pubmed-meshheading:18379416-RNA, Messenger,
pubmed-meshheading:18379416-RNA, Neoplasm,
pubmed-meshheading:18379416-Sequence Analysis, DNA,
pubmed-meshheading:18379416-Smad2 Protein,
pubmed-meshheading:18379416-Transforming Growth Factor beta,
pubmed-meshheading:18379416-Tumor Markers, Biological
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pubmed:year |
2008
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pubmed:articleTitle |
Aberrant expression of E-cadherin in lobular carcinomas of the breast.
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pubmed:affiliation |
Molecular and Cellular Pathology, Mayne Medical School, University of Queensland, Brisbane, Australia.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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