The role of E‐cadherin in low‐grade ductal breast tumourigenesis

Roylance, Rebecca; Droufakou, Stavroula; Gorman, Patricia; Gillett, Cheryl; Hart, Ian R.; Hanby, Andrew M.; Tomlinson, Ian

doi:10.1002/path.1326

Cited by 34 publications

(23 citation statements)

References 22 publications

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“…As E-cadherin is a marker of epithelial cells, loss of E-cadherin indicates the loss of the epithelial phenotype. There is evidence indicating that the germ line mutation of E-cadherin predisposes individuals to diffuse gastric and breast cancer (44)(45)(46)(47)(48). In addition to loss of E-cadherin, other EMT markers, such as vimentin, were also induced in MCF-7/Twist cells.…”

Section: Discussionmentioning

confidence: 96%

Twist Overexpression Induces In vivo Angiogenesis and Correlates with Chromosomal Instability in Breast Cancer

et al. 2005

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Aggressive cancer phenotypes are a manifestation of many different genetic alterations that promote rapid proliferation and metastasis. In this study, we show that stable overexpression of Twist in a breast cancer cell line, MCF-7, altered its morphology to a fibroblastic-like phenotype, which exhibited protein markers representative of a mesenchymal transformation. In addition, it was observed that MCF-7/Twist cells had increased vascular endothelial growth factor (VEGF) synthesis when compared with empty vector control cells. The functional changes induced by VEGF in vivo were analyzed by functional magnetic resonance imaging (MRI) of MCF-7/Twistxenografted tumors. MRI showed that MCF-7/Twist tumors exhibited higher vascular volume and vascular permeability in vivo than the MCF-7/vector control xenografts. Moreover, elevated expression of Twist in breast tumor samples obtained from patients correlated strongly with high-grade invasive carcinomas and with chromosome instability, particularly gains of chromosomes 1 and 7. Taken together, these results show that Twist overexpression in breast cancer cells can induce angiogenesis, correlates with chromosomal instability, and promotes an epithelial-mesenchymal-like transition that is pivotal for the transformation into an aggressive breast cancer phenotype. (Cancer Res 2005; 65(23): 10801-9)

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Section: Discussionmentioning

confidence: 96%

Twist Overexpression Induces In vivo Angiogenesis and Correlates with Chromosomal Instability in Breast Cancer

et al. 2005

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“…Based on their pathological and genetic features, classic LCIS and ILC are remarkably similar to those tumours in the 'low-grade arm' [2,44,47]. However, in contrast to well-differentiated DCIS/grade I IDC, the vast majority of these tumours lack Ecadherin expression owing to genetic and/or epigenetic changes in the CDH1 gene [48,[50][51][52]. On the other hand, the overlapping morphological features of PLC with both classic lobular and grade III carcinomas, and the combination of E-cadherin (16q) loss with occasional Her-2 positivity [53][54][55][56][57] add another level of complexity to these molecular pathways to breast cancer tumourigenesis.…”

Section: Invasive and In Situ Breast Carcinomasmentioning

confidence: 99%

“…In fact, the majority of neoplastic breast diseases arise from the terminal duct-lobular unit (TDLU) and so this terminology is not intended to reflect the micro-anatomical site of origin, but a difference in cell morphology [2,47]. It should also be stressed that although loss of 16q is observed in both grade I IDC and ILC, the culprit genes might differ in these two lesions [47][48][49][50][51]. The likeliest candidate gene involved in loss of 16q in atypical lobular hyperplasia (ALH)/lobular carcinoma in situ (LCIS) (see below) and ILC is CDH1 (E-cadherin), which maps to 16q22.1 [2,47,50,52,53].…”

Section: Invasive and In Situ Breast Carcinomasmentioning

confidence: 99%

“…Loss of E-cadherin, a critical cell adhesion molecule [2,47,52,53], is reflected at the morphological level by the characteristic discohesive nature of individual cells and overall growth pattern of lobular carcinomas. However, CDH1 is almost certainly not the target gene in grade I IDCs, as loss of E-cadherin expression and CDH1 gene mutations are exceedingly rare in these tumours [48]. The hunt for the gene actually involved in grade I ductal cancers is ongoing and proving exceedingly difficult [48,50,51].…”

Section: Invasive and In Situ Breast Carcinomasmentioning

confidence: 99%

“…However, CDH1 is almost certainly not the target gene in grade I IDCs, as loss of E-cadherin expression and CDH1 gene mutations are exceedingly rare in these tumours [48]. The hunt for the gene actually involved in grade I ductal cancers is ongoing and proving exceedingly difficult [48,50,51].…”

Section: Invasive and In Situ Breast Carcinomasmentioning

confidence: 99%

See 2 more Smart Citations

Molecular evolution of breast cancer

Simpson

Reis‐Filho

Gale

et al. 2005

The Journal of Pathology

453

378

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Molecular analysis of invasive breast cancer and its precursors has furthered our understanding of breast cancer progression. In the past few years, new multi-step pathways of breast cancer progression have been delineated through genotypic-phenotypic correlations. Nuclear grade, more than any other pathological feature, is strongly associated with the number and pattern of molecular genetic abnormalities in breast cancer cells. Thus, there are two distinct major pathways to the evolution of low-and high-grade invasive carcinomas: whilst the former consistently show oestrogen receptor (ER) and progesterone receptor (PgR) positivity and 16q loss, the latter are usually ER/PgR-negative and show Her-2 overexpression/amplification and complex karyotypes. The boundaries between the evolutionary pathways of well-differentiated/low-grade ductal and lobular carcinomas have been blurred, with changes in E-cadherin expression being one of the few distinguishing features between the two. In addition, lesions long thought to be precursors of breast carcinomas, such as hyperplasia of usual type, are currently considered mere risk indicators, whilst columnar cell lesions are now implicated as non-obligate precursors of atypical ductal hyperplasia (ADH) and well-differentiated ductal carcinoma in situ (DCIS). However, only through the combination of comprehensive morphological analysis and cutting-edge molecular tools can this knowledge be translated into clinical practice and patient management.

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Breast

Gudi¹,

Stamp²

2007

The Cancer Handbook

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This chapter gives an overview of the pathological changes in the breast and the current approaches to treatment and diagnosis. The micro‐anatomical structure of the breast is described in relation to pathogenesis of common benign diseases of the breast which may simulate cancer clinically. The generation of epithelial hyperplasias and definition of atypical hyperplasias (ADH and ALH) is addressed with updated classification. Emphasis is placed on the evolution of lobular and ductal in situ neoplasia and their relationships to invasive carcinoma in the main types of breast cancers are described together with the parameters used for pathological assessment. The molecular genetic and biological alterations in breast cancers are listed, and the relationship of these factors to potential diagnostic and therapeutic approaches to breast cancer are outlined.

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The role of E‐cadherin in low‐grade ductal breast tumourigenesis

Cited by 34 publications

References 22 publications

Twist Overexpression Induces In vivo Angiogenesis and Correlates with Chromosomal Instability in Breast Cancer

Twist Overexpression Induces In vivo Angiogenesis and Correlates with Chromosomal Instability in Breast Cancer

Molecular evolution of breast cancer

Breast

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