The exact process of the malignant conversion of oral submucous fibrosis (OSF) to oral cancer is not fully understood. This study aimed to detect and analyze E-cadherin expression, p63 expression, and number of mitotic figures, all correlated to cancer development, in ApoTome images of oral tissues to determine the oncogenic potentiality of OSF. ApoTome images of the study groups (6 normal, 16 OSF with dysplasia, and 10 OSF without dysplasia) were recorded. Cytoplasmic and membranous E-cadherin expression, breakages of the cell membrane, and p63 expression were detected in MATLAB 2016b. The number of mitotic figures detected by MATLAB was correlated with the number of chromosomes detected by ImageJ. A Mann–Whitney U test was done to determine a significant difference between the study groups for cytoplasmic and membranous E-cadherin distribution points. Statistical significant differences were found for cytoplasmic E-cadherin distribution between normal and OSF (with dysplasia) (p = 0.0278). There was an increase in mitotic figures, p63 expression, and cytoplasmic E-cadherin expression and a decrease in membranous E-cadherin expression from normal to diseased condition. Hence, automated detection and quantification of E-cadherin, p63, and mitotic figures in ApoTome images of oral biopsies can help in determining the oncogenic potentiality of OSF.

Maternal age dependency of gestation time in hamster and in other mammals is a well demonstrated fact. We have recently shown that adult nulliparous and multiparous hamster females show significant asynchrony and retard on early embryo development (from two blastomeres to morula stages) when compared with nulliparous young females. The number of cell–cell adhesions between blastomeres in early embryo development has been reported to be a good indication of the ability of embryos to cleave and develop. In this work we studied, by indirect immunofluorescence, the presence and distribution of E-cadherin in 4-cell embryos obtained from nulliparous young (NYF), nulliparous adult (NAF) and multiparous adult (MAF) hamster females. Distribution and intensity of fluorescence was observed and registered using confocal microscopy. Staining intensities for E-cadherin were quantified by computed densitometry in the free membrane regions, in the cytoplasm region and in the cell–cell adhesion zones of each embryo. E-Cadherin in all the studied zones was significantly higher (p < 0.01) in NYF. Cadherin concentration in the intercellular membranes was always statistically higher (p < 0.05) than in the free membrane regions. An appreciable concentration of E-cadherin was found in the cytoplasm of the 4-cell embryos obtained from the three groups of females, but was significantly higher in NYF. No statistical differences were observed in any of the parameters studied between NAF and MAF. Our results seem to indicate that changes in the reproductive behavior related to age and/or multiparity may be correlated with changes in the processes related to intercellular adhesions during early cleavage.

The mechanism that drives the growth of some colonic adenomas towards malignancy, while permitting others to remain for decades in quiescence, remains unknown. Diets can alter the growth rate of intestinal tumours but it is still unknown whether diets are able to alter the molecular biology of these adenomas in a way that predicts further outcome. To address this issue we fed Min/+ mice with two diets known to lead to different adenoma outcomes: a high-fat control diet (n 15) or a high-fat inulin-enriched (10 % w/w) diet (n 13). To study the effect of diet on cell signalling during adenoma growth, the adenomas of each Min/+ mouse were divided into three size-categories, and the levels of β-catenin, E-cadherin, cyclin D1 and matrix metalloproteinase-9, which are known to be involved in colon tumorigenesis, were determined. The growth-promoting inulin diet resulted in more large adenomas than the control feeding (P = 0·003) and doubled the total area of the adenomas (P = 0·008). The inulin diet increased the expression of nuclear β-catenin (P = 0·004) and its target cyclin D1 (P = 0·017) as the adenomas increased in size from small to large, indicating the presence of an accelerated cancerous process. Neither phenomenon was seen in the control group during adenoma growth. Our results suggest that in addition to the number, size, and growth rate of adenomatous polyps, the signalling pattern of the adenomas should also be considered when evaluating preventive dietary strategies.

β-Catenin is a multifunctional protein originally identified as a component of the cadherin cell-cell adhesion complex. It also binds the adenomatous polyposis coli (APC) tumour suppressor which controls β-catenin cellular levels through its degradation. β-Catenin and/or APC mutations result in increased cytoplasmic β-catenin and nuclear translocation. The aim of the present study was to examine the expression and cellular localisation of α- and β-catenin, pi20 and E-cadherin in a chemically-induced mouse model of colo-rectal cancer using 1,2-dimethylhydrazine (DMH). Female Balb/C mice were injected subcutaneously with a solution providing 25 mg DMH base/kg body weight for 17 weeks. Animals were killed and tumours identified in the intestine with a dissecting microscope. Formalin-fixed paraffin-embedded sections of normal and dysplastic colonic mucosa were stained by an indirect avidin-biotin immunohistochemical technique using mouse monoclonal antibodies, and membranous, cytoplasmic and nuclear cellular localisation was assessed by light microscopy. Staining distribution scored as follows: 3, >90% positive epithelial cells; 2, >50% positive epithelial cells; 1, <50% positive epithelial cells. Non-dysplastic colonic epithelial cells revealed p-catenin expression at the membrane (33/41 scored 3), areas of cytoplasmic expression (24/41 scored 1) and no nuclear staining. Dysplastic colonic epithelium revealed increased membranous and cytoplasmic p-catenin immunoreactivity (39/41 and 38/41 both scored 3) with focal nuclear staining (14/41). Expression patterns for a-catenin, pi20, and E-cadherin were similar to β-catenin with increased membranous and cytoplasmic immunoreactivity in dysplastic mucosa, although no nuclear staining was observed. Increased cytoplasmic expression and nuclear localisation of β-catenin are consistent with a possible mutation in its gene, and this finding was in keeping with the mutational analysis of exon 3 by single-strand conformational polymorphism. Increased immunoreactivity of the other catenins also suggests further disruption in catenin regulation. In summary, alterations in the β-catenin expression and cellular localisation in the DMH-induced tumours are similar to those seen in human sporadic colo-rectal tumours. The DMH is therefore a useful model for studying the abnormalities of the E-cadherin-catenin pathway in colo-rectal carcinogenesis.

Objectives: To investigate the topography of E-cadherin and its possible correlation with the histological phenotype of salivary gland tumours.

Material and methods: Archival formalin-fixed, paraffin-embedded sections of 54 benign and 56 malignant tumours and 24 samples of normal and inflamed salivary gland tissue were studied immunohistochemically using an Envision/horseraddish peroxidase (HRP) technique.

Results: In normal and inflamed salivary gland samples, E-cadherin was expressed at the membrane of acinar, myoepithelial and ductal cells located at cell–cell contact points. Reduction and/or absence of E-cadherin was only observed in pleomorphic adenoma at the peripheral cells of the duct-like or island structures, or in the cells exhibiting plasmacytoid or stromal differentiation. Neoplastic epithelium in Warthin's tumours and in myoepithelial and oncocytic adenomas was strongly positive. Furthermore, a weak to moderate loss of expression which was related to tissue tumour subtype was seen in malignant tumours such as: adenoid cystic carcinomas; polymorphous low-grade adenocarcinomas; acinic cell carcinomas; and mucoepidermoid low-grade, epithelial-myoepithelial, lymphoepithelial and squamous low-grade carcinomas. Moderate to extreme loss or alternative cytoplasmic non-functional expression were observed in cases of salivary ductal carcinoma, carcinosarcoma, myoepithelial carcinoma, oncocytic adenocarcinoma, unspecified adenocarcinoma and squamous high-grade carcinomas.

Conclusion: This study suggests a direct association of E-cadherin expression with neoplastic histologic phenotype, which is lost in the more undifferentiated and invasive epithelial salivary gland tumours.

Upper gastrointestinal (GI) tract malignancies, including carcinomas of the esophagus, the GI junction and the stomach, are among the most common cancers worldwide. Overall survival is poor because many patients present with locally advanced and often incurable disease. This review focuses on the pathogenesis of adenocarcinomas of the stomach. It summarises recent findings on genetic predisposition to gastric cancer, in particular in relation to germline mutations in the E-cadherin gene. It also describes the molecular basis of sporadic gastric cancer, including alterations in oncogenes, tumour suppressor genes and growth factors, and discusses how these findings might be used in the clinic for improved diagnosis and therapy.

To define better the function of Nerve Growth Factor (NGF) in breast cancer progression, we investigated whether this polypeptide was able to induce breast cancer cell invasion. NGF inhibited aggregation of tumour cells through modulation of the E-cadherin/catenin complex function. In addition, NGF induced the breast cancer cells to invade into Matrigel. We focused our attention on how NGF prevents aggregation, in order to discover the signalling pathway that leads tumour cells to acquire the invasive phenotype. Moreover, studies on the identification of signalling pathways that are responsive for NGF-induced invasion will be basically described.

Numerous studies suggest that loss of E-cadherin is necessary to induce Epithelial–mesenchymal transition (EMT) and metastasis. Snail is a major contributor to EMTs. The Snail family of zinc-finger transcription factors interact with the E-cadherin promoter to repress transcription during EMT. The present article reviews the regulation of E-cadherin and discusses recent novel insights into the molecular basis in the process of EMT.

Development of desmin-positive hepatic stellate cells was studied in mice using double immunofluorescent techniques and in vitro cultures with special attention given to their cell lineages. Several studies recently reported on the presence of cells that are immunologically reactive with both antidesmin and anticytokeratin antibodies in young fetal rat livers, and suggested the possibility that these cells give rise to hepatocytes and hepatic stellate cells. At early stages of mouse liver development, stellate cells with desmin-positive filaments were scattered in the liver parenchyma. However, the stellate cells definitely differed from hepatoblasts and hepatocytes in terms of their morphology and expression of desmin and hepatoblast and hepatocyte-specific E-cadherin in the liver. Fetal hepatoblasts and hepatocytes did not react with antidesmin antibodies, nor did desmin-positive stellate cells express E-cadherin in vivo and in vitro. Thus it is likely that desmin-positive stellate cells and hepatoblasts belong to different cell lineages. In the fetal liver, the desmin-positive stellate cells surrounded blood vessels, and extended their processes to haematopoietic cells and megakaryocytes. Many, but not all, hepatoblasts and hepatocytes were observed to be associated with the stellate cells. At fetal stages, cellular processes positive for desmin in the stellate cells were also thick compared with those in the adult liver, in which desmin-positive stellate cells lay in Disse's space and were closely associated with all hepatocytes. These developmental changes in the geography of desmin-positive cells in the liver parenchyma and their morphology may be associated with their maturation and interactions with other cell types.

It has been reported that infection with Nippostrongylus brasiliensis induces villus atrophy with various histological alterations. In N. brasiliensis-infected rats, villus length in the jejunum was reduced significantly at day 10 p.i., when serum levels of rat mast cell protease (RMCP) II had increased significantly. To determine whether the villus atrophy is associated with enhancement of apoptosis, apoptotic nuclei were labelled using the nick end-labelling method. Numbers of labelled cells were markedly increased in the villus epithelium at 7–10 days p.i., while the numbers returned to normal 14 days p.i. when worms were rejected from the intestine and villus length became normal. Examination of the expression of the adhesion molecule E-cadherin showed granular immunoreactivity in the cytoplasm of atrophic villus epithelium with loss of normal localization to epithelial cell borders. In mast cell-deficient Ws/Ws rats, villus length was reduced as significantly as in +/+ counterparts at day 10 p.i. with marked increases in the numbers of apoptotic cells. These results suggested that villus atrophy was closely associated with enhanced apoptosis and loss of adhesion in epithelial cells. Mast cell activation appears not to be involved in these alterations.