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Cluster analysis of claudin‐1 and ‐4, E‐cadherin, and β‐catenin expression in colorectal cancers
Author(s) -
Matsuoka Takashi,
Mitomi Hiroyuki,
Fukui Naoshi,
Kanazawa Hideki,
Saito Tsuyoshi,
Hayashi Takuo,
Yao Takashi
Publication year - 2011
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.21854
Subject(s) - claudin , catenin , cadherin , hazard ratio , medicine , immunohistochemistry , colorectal cancer , cell adhesion molecule , oncology , stage (stratigraphy) , proportional hazards model , multivariate analysis , pathology , confidence interval , cancer research , cancer , biology , cell , tight junction , immunology , wnt signaling pathway , gene , genetics , paleontology
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 β‐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 β‐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 β‐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 β‐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. © 2011 Wiley‐Liss, Inc.