Downregulation of Plasma Membrane
Expression/Cytoplasmic Accumulation of
Beta-Catenin Predicts Shortened Survival in
Non-Small Cell Lung Cancer
A Clinicopathologic Study of 100 Cases
Křen L.1, Hermanová M. 1, Goncharuk V. N.2, Kaur P.3, Ross, J. S.3,Pavlovský Z.4, Dvořák K.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, Czech Republic |
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Summary:
The E-cadherin-catenin complex proteins function in cell-cell adhesion and have been reported to
be dysregulated in various human malignancies. Beta catenin is a cytoplasmic protein that associates
with tyrosine kinase receptors and modulates cytoskeletal dynamics. It also plays a role in
the Wnt signaling pathway. During neoplastic transformation, the phosphorylation of beta-catenin
causes 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 immunostained
with a monoclonal beta-catenin antibody. There were 47 squamous cell carcinomas (SCC) and 53
adenocarcinomas (AC) in the study group. Plasma membrane/cytoplasmic beta-catenin immunoreactivity
was scored for intensity and distribution and correlated with tumor stage, grade and
survival. Plasma membrane/cytoplasmic immunoreactivity for beta-catenin protein was observed
in 71 (71%) of 100 NSCLC. 44 (94%) of 47 SCC and 27 (51%) of 53 AC expressed beta catenin. On
univariate 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 expression
associated with high grade NSCLC reached near significance (p=0.07). On multivariate analysis,
the loss of beta catenin expression independently predicted shortened overall patient survival
in NSCLC (p=0.05). Beta catenin expression loss is associated with advanced tumor stage and is an independent
predictor of shortened patient survival in NSCLC.
Key words:
beta-catenin - non-small cell lung cancer - survival
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