Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2008-4-28
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1532-0979
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
32
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
773-83
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
pubmed:year
2008
pubmed:articleTitle
Aberrant expression of E-cadherin in lobular carcinomas of the breast.
pubmed:affiliation
Molecular and Cellular Pathology, Mayne Medical School, University of Queensland, Brisbane, Australia.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't