E-CADHERIN IMMUNOHISTOCHEMICAL

E-cadherin Immunohistochemical



Abstract

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.

Table of Content

Abstract2

Introduction4

Results5

E-cadherin5

ß-catenin5

Discussion9

Conclusion13

References15

E-cadherin Immunohistochemical

Introduction

E-cadherin is a regulator of the differentiated epithelial cell phenotype, with key roles in the formation of cell adherens junctions and the establishment of epithelial polarity. Mutation or abnormal expression of E-cadherin is known to be carcinogenic in a variety of epithelial tissues. The OSE is continuous with the mesothelium covering the peritoneal cavity and is therefore better classified as a mesothelium, rather than a true epithelium . Normal OSE and peritoneal mesothelial cells express little to no E-cadherin, but transformed OSE cells and cells from primary epithelial ovarian cancer (EOC) have increased E-cadherin expression.

E-cadherin is a crucial transmembrane glycoprotein which is implicated in the mediation of calcium-dependent cell-cell adhesion through homophilic interactions and in the controlling of cell polarity and morphogenesis. Through its intracellular cytoplasmic domain, E-cadherin interacts via catenins with F-actin and, therefore, has a role in mediating the cytoskeleton and cell motility. Via its extracellular domain, E-cadherin is associated with zipper mediating cell-cell adhesion. In the context of tumor progression, down-regulation of E-cadherin has been associated with tumor cell infiltration and metastasis.

Lobular carcinoma in situ (LCIS) and invasive lobular carcinoma (ILC) have different biologic and clinical significance to their more commonly diagnosed counterparts ductal carcinoma in situ (DCIS) and invasive ductal carcinoma (IDC). For instance, patients diagnosed with LCIS may be managed by clinical follow-up with mammography, clinical follow-up alone, tamoxifen, or simply no action. In contrast, DCIS is treated with wide local excision, excision and radiation therapy, or ...