Downregulation of Plasma MembraneExpression/Cytoplasmic Accumulation ofBeta-Catenin Predicts Shortened Survival inNon-Small Cell Lung CancerA Clinicopathologic Study of 100 Cases

Overview

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.

Key words:
beta-catenin - non-small cell lung cancer - survival