Downregulation of Plasma MembraneExpression/Cytoplasmic Accumulation ofBeta-Catenin Predicts Shortened Survival inNon-Small Cell Lung CancerA Clinicopathologic Study of 100 Cases
L. Křen 1; M. Hermanová 1; V. N. Goncharuk 2; P. Kaur 3; J. S. Ross 3; Z. Pavlovský 4; K. Dvořák 1
From the Departments of Pathology: 1The University Hospital Brno, Czech Republic 2The University of Texas M. D. Anderson Cancer Center, Houston, Texas, U. S. A. 3The Albany Medical College, Albany, U. S. A. 4The Masaryk Memorial Cancer Institute, Brno, Cz
Čes.-slov. Patol., , 2003, No. 1, p. 17-20
The E-cadherin-catenin complex proteins function in cell-cell adhesion and have been reported tobe dysregulated in various human malignancies. Beta catenin is a cytoplasmic protein that associateswith tyrosine kinase receptors and modulates cytoskeletal dynamics. It also plays a role inthe Wnt signaling pathway. During neoplastic transformation, the phosphorylation of beta-catenincauses a loss of intercellular adhesions resulting in increased tumor cell motility and invasiveness.Tissue sections from 100 cases of non-small cell lung cancer (NSCLC) were immunostainedwith a monoclonal beta-catenin antibody. There were 47 squamous cell carcinomas (SCC) and 53adenocarcinomas (AC) in the study group. Plasma membrane/cytoplasmic beta-catenin immunoreactivitywas scored for intensity and distribution and correlated with tumor stage, grade andsurvival. Plasma membrane/cytoplasmic immunoreactivity for beta-catenin protein was observedin 71 (71%) of 100 NSCLC. 44 (94%) of 47 SCC and 27 (51%) of 53 AC expressed beta catenin. Onunivariate analysis, loss of beta catenin expression correlated with high tumor stage (p=0.025),large tumor size (p=0.02) and decreased patient survival (p=0.04). The loss of beta catenin expressionassociated with high grade NSCLC reached near significance (p=0.07). On multivariate analysis,the loss of beta catenin expression independently predicted shortened overall patient survivalin NSCLC (p=0.05). Beta catenin expression loss is associated with advanced tumor stage and is an independentpredictor of shortened patient survival in NSCLC.
beta-catenin - non-small cell lung cancer - survival
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