Cluster Analysis of Claudin-1 and-4, E-Cadherin, and β-Catenin Expression in Colorectal Cancers

Background and Objectives: Intercellular adhesion mediated by the claudin and cadherin/catenin complex is a prerequisite for epithelial integrity and differentiation, and has been suggested to be frequently disturbed in cancers. The aim of this study was to assess the relationship between such abnormality and clinicopathological features of colorectal carcinomas. Methods: Immunohistochemical analysis of claudin-1 and -4, E-cadherin, and beta-catenin was performed on a series of 156 cases. Results: Significant positive associations (P < 0.05-0.001) were found with immunoreactivity for each except nuclear beta-catenin. Reduced expression was correlated with poor tumor differentiation (claudin-1, P = 0.035; claudin-4, P = 0.011; E-cadherin, P < 0.001; membranous beta-catenin, P = 0.002), an advanced TNM stage (claudin-1, P = 0.002; claudin-4, P = 0.008), and a poor prognosis. On multivariate analysis, reduced expression of E-cadherin (P < 0.001) and beta-catenin (P = 0.048) at invasive fronts proved to be an independent predictor of short survival. Hierarchical cluster analysis identified three distinct groups with a good, intermediate, and poor prognosis, having an independent survival outcome by multivariate analysis (good or intermediate vs. poor: hazard ratio, 2.66; 95% confidence interval, 1.54-4.60; P < 0.001). Conclusions: Disruption of cell adhesion molecules correlates with tumor differentiation and progression in colorectal carcinomas. Specific marker profiles were identified here as independent prognostic indicators. J. Surg. Oncol. 2011;103:674-686. (C) 2011 Wiley-Liss, Inc.