Wnt/ß-Catenin Signaling as a Molecular Target by Pathogenic Bacteria.

The Wnt/ß-catenin signaling pathway is crucial to regulate cell proliferation and polarity, cell determination, and tissue homeostasis. The activation of Wnt/ß-catenin signaling is based on the interaction between Wnt glycoproteins and seven transmembrane receptors-Frizzled (Fzd). This binding promotes recruitment of the scaffolding protein Disheveled (Dvl), which results in the phosphorylation of the co-receptor LRP5/6. The resultant molecular complex Wnt-Fzd-LRP5/6-Dvl forms a structural region for Axin interaction that disrupts Axin-mediated phosphorylation/degradation of the transcriptional co-activator ß-catenin, thereby allowing it to stabilize and accumulate in the nucleus where it activates the expression of Wnt-dependent genes. Due to the prominent physiological function, the Wnt/ß-catenin signaling must be strictly controlled because its dysregulation, which is caused by different stimuli, may lead to alterations in cell proliferation, apoptosis, and inflammation-associated cancer. The virulence factors from pathogenic bacteria such as Salmonella enterica sv Typhimurium, Helicobacter pylori, Mycobacterium tuberculosis, Pseudomonas aeruginosa, Citrobacter rodentium, Clostridium difficile, Bacteroides fragilis, Escherichia coli, Haemophilus parasuis, Lawsonia intracellularis, Shigella dysenteriae, and Staphylococcus epidermidis employ a variety of molecular strategies to alter the appropriate functioning of diverse signaling pathways. Among these, Wnt/ß-catenin has recently emerged as an important target of several virulence factors produced by bacteria. The mechanisms used by these factors to interfere with the activity of Wnt/ß-catenin is diverse and include the repression of Wnt inhibitors' expression by the epigenetic modification of histones, blocking Wnt-Fzd ligand binding, activation or inhibition of ß-catenin nuclear translocation, down- or up-regulation of Wnt family members, and inhibition of Axin-1 expression that promotes ß-catenin activity. Such a variety of mechanisms illustrate an evolutionary co-adaptation of eukaryotic molecular signaling to a battery of soluble or structural components synthesized by pathogenic bacteria. This review gathers the recent efforts to elucidate the mechanistic details through which bacterial virulence factors modulate Wnt/ß-catenin signaling and its physiological consequences concerning the inflammatory response and cancer.

Immunohistochemistry applied to the differential diagnosis between ductal and lobular carcinoma of the breast.

The distinction between classic lobular and ductal carcinoma, both in situ and invasive, has important therapeutic and management implications. Most ductal and lobular carcinomas are distinguished readily on hematoxylin-eosin-stained sections because of distinct histomorphologic features. In cases with ambiguous morphologic features, however, categorization in one or another type can be a challenge. Several immunohistochemical markers, including epithelial cadherin, p120, ß-catenin, and low-molecular-weight and high-molecular-weight cytokeratins among others, have been introduced to help better discriminate between lobular neoplasia and ductal carcinoma. In this critical review of the literature, we comment about the usefulness and the limitations of these markers to improve the accuracy in the differential diagnosis of breast pathology.

Beta-catenin and E-cadherin tissue "content" as prognostic markers in left-side colorectal cancer.

AIM: To investigate the relationship between beta-catenin and E-cadherin tissue quantitative expression (content) in tumors and clinical prognostic factors in patients with left colon cancer. MATERIAL AND METHODS: Twenty nine patients with colon adenocarcinoma located distal to the splenic flexure were studied. Diagnosis and histological variables related to adenocarcinoma prognosis were evaluated using hematoxylin-eosin. Beta-catenin and E-cadherin were analysed by immunohistochemistry with specific anti-beta-catenin and anti-E-cadherin monoclonal antibodies. Tissue quantitative expression (content) was determined by computer assisted image analysis method. Results were analysed with statistical tests, adopting a significance level of 5%. RESULTS: There are correlations between beta-catenin and TNM stage (p< 0.01). There are progressively greater amounts of beta-catenin in patients with deeper invasion of the tumor in colon layers (p=0.03), progressive lymph node involvement (p=0.05), as well as in patients with distant metastasis (p=0.04). Worse histological grades are related to lower expression of E-cadherin in tumor tissue (p=0.01). CONCLUSIONS: E-cadherin can be used as an indicator of tumor differentiation degree, whereas beta-catenin can be used as a predictor of invasion depth and spread of distal colorectal cancer.