Clinicopathological features and epidermal growth factor receptor mutations associated with epithelial-mesenchymal transition in non-small cell lung cancer

Respirology. 2009 Apr;14(3):371-6. doi: 10.1111/j.1440-1843.2009.01496.x.

Abstract

Background and objective: Small molecular inhibitors of the epidermal growth factor receptor (EGFR) have been extensively studied in non-small cell lung cancer (NSCLC) patients. The discovery of molecular biomarkers that identify the subgroups of NSCLC patients benefiting from EGFR tyrosine kinase inhibitor (TKI) has become an important area of investigation. Recent studies have suggested that epithelial-mesenchymal transition (EMT) in tumours decreases the cellular requirements for EGFR signalling pathway, and this may provide a molecular signature to define those NSCLC patients most likely to respond to treatment with targeted EGFR TKI. This research explored the clinicopathological features and EGFR mutations associated with EMT in NSCLC.

Methods: The EMT status in surgically resected specimens from 62 patients with NSCLC was tested by immunohistochemical staining. The frequency of tumour epithelial phenotype was calculated and the strength of the association with clinicopathological features and EGFR genotype was determined by logistic regression.

Results: The overall frequency of the epithelial phenotype was 35.48% (22 of 62). Based on univariate analyses, the frequency of the epithelial phenotype (E-cadherin-positive) was greater for EGFR mutants versus wild types (77.78% vs 18.18%; P < 0.0001) and women versus men (54.55% vs 25%; P = 0.02). Multivariate logistic analysis showed that only the EGFR genotype (odds ratio, 0.063; 95% CI: 0.013-0.3; P = 0.0005) was significantly associated with the epithelial phenotype.

Conclusion: In patients with NSCLC, there is a higher frequency of epithelial markers in patients with EGFR mutation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Cadherins / metabolism
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Transformation, Neoplastic / genetics*
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / therapeutic use
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • ErbB Receptors / genetics*
  • Female
  • Genotype
  • Humans
  • Logistic Models
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Male
  • Mesoderm / metabolism
  • Mesoderm / pathology
  • Middle Aged
  • Multivariate Analysis
  • Mutation / genetics*
  • Neoplasm Staging
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Vimentin / metabolism

Substances

  • Cadherins
  • Enzyme Inhibitors
  • Vimentin
  • ErbB Receptors
  • Protein-Tyrosine Kinases