Aberrant expression of E-cadherin in lobular carcinomas of the breast

DA Silva, L, Parry, S, Reid, L, Keith, P, Waddell, N, Kossai, M, Clarke, C, Lakhani, SR and Simpson, PT (2008) Aberrant expression of E-cadherin in lobular carcinomas of the breast. American Journal of Surgical Pathology, 32 5: 773-783.


Author DA Silva, L
Parry, S
Reid, L
Keith, P
Waddell, N
Kossai, M
Clarke, C
Lakhani, SR
Simpson, PT
Title Aberrant expression of E-cadherin in lobular carcinomas of the breast
Journal name American Journal of Surgical Pathology   Check publisher's open access policy
ISSN 0147-5185
Publication date 2008-05
Sub-type Article (original research)
DOI 10.1097/PAS.0b013e318158d6c5
Volume 32
Issue 5
Start page 773
End page 783
Total pages 11
Place of publication Hagerstown, MD , U.S.A.
Publisher Lippincott, Williams & Wilkins
Collection year 2009
Language eng
Subject C1
110316 Pathology (excl. Oral Pathology)
920102 Cancer and Related Disorders
Abstract AB 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. (C) 2008 Lippincott Williams & Wilkins, Inc.
Keyword Breast cancer
E-cadherin
B-catenin
DASL gene expression profiling
Lobular carcinoma
Q-Index Code C1
Q-Index Status Confirmed Code

 
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Created: Thu, 05 Mar 2009, 15:18:13 EST by Brenda Mason on behalf of UQ Centre for Clinical Research