The Mesenchymal State Predicts Poor Disease-Free Survival in Resectable Non-Small Cell Lung Cancer

Ann Thorac Surg. 2017 Jul;104(1):321-328. doi: 10.1016/j.athoracsur.2017.01.091. Epub 2017 May 9.


Background: The epithelial-mesenchymal transition (EMT) is thought to contribute to the overall invasiveness of malignant cells. Expression of cluster of differentiation (CD) 44 and CD90 mark the mesenchymal state in multiple epithelial malignancies. Their role in lung cancer remains unclear, however. This study evaluated the prognostic significance of CD44 and CD90 coexpression in patients with resectable primary non-small cell lung cancer (NSCLC).

Methods: This was a nonconcurrent cohort study of patients with resectable NSCLC, stratified by the degree of expression of CD44/CD90 double-positive cells in their primary tumor. Flow cytometry was used for immunophenotyping of freshly isolated disaggregated tumor. We analyzed the relationship between expression of CD44/CD90 and relapse-free survival.

Results: We evaluated 37 patients (18 men; median age, 70 years) with NSCLC. For this group, the geometric mean proportion of cells coexpressing CD44/CD90 was 0.52%. Expression of CD44/CD90 was significantly elevated (24.4%, geometric mean) in 6 patients. The median relapse-free survival for patients with high CD44/CD90 coexpression was 7.7 months (95% confidence interval, 4.2 to 11.7) compared with 40 months (95% confidence interval, 18.2 to 77.8) for the group with low CD44/CD90 coexpression (p = 0.00006 by Mantel log-rank test). The assessment of risk based upon CD44/CD90 expression status was not correlated with pathologic staging (p = 0.073 by χ2).

Conclusions: High expression of CD44 and CD90 was associated with significantly reduced relapse-free survival in NSCLC patients. These results suggest that CD44 and CD90 may be important markers of tumor progression in NSCLC.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Disease-Free Survival
  • Epithelial-Mesenchymal Transition*
  • Female
  • Flow Cytometry
  • Humans
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology*
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Neoplastic Stem Cells / pathology*
  • Pneumonectomy*
  • Prognosis
  • Survival Rate / trends
  • United States / epidemiology