Gene mutations in squamous cell NSCLC: insignificance of EGFR, KRAS and PIK3CA mutations in prediction of EGFR-TKI treatment efficacy

Anticancer Res. 2013 Apr;33(4):1705-11.

Abstract

Background: Epidermal growth factor receptor (EGFR), Kirsten rat sarcoma viral oncogene (KRAS) and phosphatidylinositide-3-kinase catalytic subunit-alpha (PIK3CA) mutations are biomarkers used for the prediction of efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs) in advanced non-small cell lung cancer (NSCLC).

Patients and methods: In total, 223 patients with advanced-stage squamous cell NSCLC were tested; 179 patients were treated with EGFR-TKIs. Genetic testing was performed using a combination of denaturing capillary electrophoresis and direct Sanger sequencing.

Results: EGFR mutations were detected in 7.2%; KRAS mutations in 7.4% and PIK3CA mutations in 3.8% of patients. No correlation of EGFR or PIK3CA mutation status with progression-free survival (PFS) (p=0.425; p=0.197), nor overall survival (OS) (p=0.673; p=0.687), was observed. KRAS mutations correlated with shorter OS (p=0.039), but not with PFS (p=0.120).

Conclusion: We did not observe any role of EGFR, KRAS, PIK3CA mutations in prediction of EGFR-TKIs efficacy in patients with advanced-stage squamous cell NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / mortality
  • Carcinoma, Squamous Cell / drug therapy
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / mortality
  • Class I Phosphatidylinositol 3-Kinases
  • Drug Resistance, Neoplasm
  • ErbB Receptors / genetics*
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Staging
  • Phosphatidylinositol 3-Kinases / genetics*
  • Prognosis
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Retrospective Studies
  • Survival Rate
  • ras Proteins / genetics*

Substances

  • KRAS protein, human
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins