Epithelial (E‐) and placentae (P‐) cadherin cell adhesion molecule expression in breast carcinoma

Abstract

Two members of the cadherin family of intercellular adhesion molecules are found in normal breast tissue: E-(epithelial) cadherin is present in both luminal and myoepithelial cells, whereas P- (placental) cadherin is confined to myoepithelium. There is experimental evidence that loss of E-cadherin is associated with increased invasiveness of malignant cells in vitro, which stimulated us to examine the presence and distribution of E- and P-cadherin in breast carcinomas by means of immunohistochemical staining. E-Cadherin was present in all in situ and invasive ductal carcinomas examined, although it had a patchy distribution and the staining was of variable intensity. However, in 83 per cent of invasive lobular carcinomas and all lobular carcinomas in situ there was complete loss of E-cadherin expression. In the remaining 17 per cent of invasive lobular tumours, E-cadherin appeared to have an abnormal distribution within the cytoplasm with variable expression on the cell membrane. P-Cadherin, by contrast, was absent from all benign breast luminal epithelium and 25 carcinomas of ductal and lobular type. It was found in only one carcinoma of lobular type. We suggest that loss of cell-cell adhesion mediated by E-cadherin plays a part in the characteristic morphology of lobular carcinomas.

E-cadherin as a prognostic indicator in primary breast cancer

“…Most series (whether using frozen or fixed tissue), including the present one, have shown that the epithelial cells of normal ducts stain strongly and clearly around the membrane (Gamallo et al, 1993;Moll et al, 1993;Rasbridge et al, 1993;Birchmeier and Behrens 1994;Hashizume et al, 1996;Gupta et al, 1997;Hunt et al, 1997). Oku et al (1993) noted that 80% of frozen tumour sections with reduced E-CD expression were heterogeneous (Oka et al, 1993).…”

“…We did not evaluate cytoplasmic staining in addition to membrane staining, as it was assumed that any E-CD protein present in the cytoplasm was non-functional. However, other studies have described E-CD cytoplasmic staining based on the hypothesis that it may be new protein stored in the Golgi apparatus or internalised for some reason (Rasbridge et al, 1993). Alternatively, as cytoplasmic staining tends to be seen in tumours with some loss of E-CD expression, there may be a defect in transport mechanisms moving the protein to the membrane.…”

“…Epithelial cadherin (E-cadherin) is a member of the cadherin family of cell adhesion molecules, joining adjacent epithelial cells together via a Ca 2+ -dependent homophilic binding mechanism (Rasbridge et al, 1993). The cytoplasmic domain of E-cadherin (E-CD) complexes with cytoplasmic proteins known as catenins, which links the cadherin with the cytoskeleton and other transmembrane proteins (Kemler, 1993).…”

“…E-CD expression in ductal carcinoma in situ (DCIS) is similar to that of normal tissue, while invasive ductal carcinomas may have reduced or heterogeneous expression. In contrast, infiltrating lobular carcinoma (ILC) has significantly reduced or absent expression (Gamallo et al, 1993;Oka et al, 1993;Rasbridge et al, 1993;Birchmeier and Behrens, 1994;Lipponen et al, 1994;Siitonen et al, 1996;Charpin et al, 1997;Gonzalez et al, 1999). The reduced expression seen in ILC is assumed to be reflected in the different pattern of invasion compared to ductal and special types of breast cancer.…”

BRCA1 and GATA3 corepress FOXC1 to inhibit the pathogenesis of basal-like breast cancers

“…GATA3 siRNA knockdown in T47D luminal breast cancer cells resulted in increased expression of a number of previously reported basal/myoepithelial markers including FOXC2, p-cadherin and CXCL1 (Rasbridge et al, 1993;Mani et al, 2007;Bierie et al, 2008) (Figure 5b (i)). Conversely, exogenous GATA3 expression in basal-like SUM149 cells resulted in downregulation of these same markers (Figure 5b (ii)).…”