E-cadherin expression in primary carcinomas of the breast and its distant metastases

Abstract

IntroductionTumor invasion with subsequent metastases is the major cause of morbidity and mortality in patients with cancer. For patients with breast cancer, the development of metastases is the most important prognostic factor, as almost all patients with distant metastasis succumb to the disease [1][2][3].Numerous studies have linked aberrant expression of E-cadherin with the development of metastases in breast cancer and other cancers. E-cadherin is a transmembrane glycoprotein that mediates calcium-dependent intercellular adhesion and is specifically involved in epithelial cell-tocell adhesion [4][5][6]. The E-cadherin gene, located on chromosome 16q22.1, is an important regulator of morphogenesis [7,8]. In cancer, decreased E-cadherin expression is one of the alterations that characterizes the invasive phenotype, and the data support its role as a tumor suppressor gene [9][10][11][12] Normal ductal epithelial cells in the mammary gland strongly express E-cadherin protein in the cytoplasmic membrane [21,22]. Some studies in breast cancer have ER = estrogen receptor; PR = progesterone receptor. Kowalski et al., licensee BioMed Central Ltd (Print ISSN 1465-5411; Online ISSN 1465-542X). This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL. AbstractIntroduction Aberrant expression of E-cadherin has been associated with the development of metastases in patients with breast cancer. Even though the expression of E-cadherin has been studied in primary breast tumors, little is known about its expression at the distant metastatic sites. We investigate the relationship between E-cadherin expression in primary breast carcinoma and their distant, non-nodal metastases.

Expression of E-Cadherin in breast carcinomas and its association with other biological markers — a prospective study

“…However, somatic mutations in E-CD gene have been found in only 56% ILCs (14). Cytoplasmic positivity, as noticed in two cases of ILC in present study, has also been reported by other workers 30,31 This different pattern of E-CD expression in invasive ductal and lobular carcinomas suggests that this protein molecule plays different role in the two morphologic types. In cases of ductal carcinomas with lobular differentiation, we observed a mixed pattern of staining.…”

“…Thirty-five percent cases showed positive E-CD staining in the deposits. Similar observations were reported in distant metastatic tumor deposits by Kowalski et al 30 There is growing evidence that carcinoma cells, which loose E-CD expression, may re-express it once 45 they reach distant sites. Underlying reasons for this re-expression might be related to the fact that tumor cells require to gain certain molecules that would enable them to adhere to different stromal components and endothelial cells at foreign sites, which they loose at the time of being uprooted from primary site, where the expression gets lost.…”

“…This direct association was found to be 51% after accounting for chance agreement. While, Lipponen et al 39 demonstrated a similar direct association of E-CD expression with ER protein expression, other workers 30,40 did not observe any significant association between the two. It has been postulated that reversible down regulation of E-CD may occur by hypermethylation of the promoter region of E-CD expression.…”

Novel retinoic acid metabolism blocking agents have potent inhibitory activities on human breast cancer cells and tumour growth

“…Further support for the putative role of our RAMBAs as differentiating agents came from the findings that VN/14-1 caused a dose-dependent up-modulation (from four-to six-fold) of ER-a protein, another differentiation marker. The ability of these RAMBAs to induce differentiation in breast cancer cells may be of significance in light of recent findings which suggest that downregulated expressions of CK 18 (Korsching et al, 2002;Woelfle et al, 2004;Schaller and Buhler, 2005) and/or E-cadherin/ ER-a (Nass et al, 2000;Kowalsski et al, 2003) promote progression of human breast cancer. It should be noted that differentiated tumour cells exhibit low proliferative and metastatic potential.…”

E-cadherin inhibits tumor cell growth by suppressing PI3K/Akt signaling via β-catenin-Egr1-mediated PTEN expression

“…On the other hand, the expression of E-cadherin supports cohesive, collective cell migration/ invasion (Friedl and Gilmour, 2009). Although the loss of E-cadherin expression or function is a common event in tumor progression (Yap, 1998;Nollet et al, 1999), there is emerging evidence that the expression of E-cadherin during cancer progression may be dynamic and highly contextual (Kowalski et al, 2003). To date, E-cadherin regulates PTEN via b-catenin-Egr1 signaling M-T Lau et al the role of E-cadherin in ovarian cancer progression remains controversial, particularly in regards to its effects on cell growth.…”