title: 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.
abstract: 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.
authors.affiliation: Department of Pathology, University Hospital Brno, Czech Republic.
authors.forename: L
authors.initials: L
authors.lastname: Kren
authors.forename: M
authors.initials: M
authors.lastname: Hermanová
authors.forename: V N
authors.initials: VN
authors.lastname: Goncharuk
authors.forename: P
authors.initials: P
authors.lastname: Kaur
authors.forename: J S
authors.initials: JS
authors.lastname: Ross
authors.forename: Z
authors.initials: Z
authors.lastname: Pavlovský
authors.forename: K
authors.initials: K
authors.lastname: Dvorák
mesh_terms: D000230:Adenocarcinoma / Q000737:chemistry / Q000401:mortality; D015820:Cadherins / Q000032:analysis; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry / Q000401:mortality*; D002294:Carcinoma, Squamous Cell / Q000737:chemistry / Q000401:mortality; D002462:Cell Membrane / Q000737:chemistry; D003593:Cytoplasm / Q000737:chemistry; D003598:Cytoskeletal Proteins / Q000032:analysis*; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry / Q000401:mortality*; D008297:Male; D015996:Survival Rate; D015534:Trans-Activators / Q000032:analysis*; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D015534:Trans-Activators; D051176:beta Catenin