PTEN and PIK3CA expression is associated with prolonged survival after gefitinib treatment in EGFR-mutated lung cancer patients

J Thorac Oncol. 2006 Sep;1(7):629-34.


Background: We and other researchers have previously reported that pulmonary adenocarcinomas with epidermal growth factor receptor (EGFR) mutations are usually sensitive to gefitinib, an EGFR-specific tyrosine kinase inhibitor, although this relationship is not complete. In this study, we searched for mutations or changes in the expression of genes downstream to EGFR and evaluated their relationship with the effectiveness of gefitinib.

Methods: We studied 78 lung cancer patients who had recurrent disease after surgical resection and were treated with gefitinib. We searched for mutations occurring in the KRAS and PIK3CA gene. We also evaluated the expression level of EGFR, PIK3CA, and PTEN by real-time reverse transcriptase polymerase chain reaction. Gefitinib effectiveness was evaluated by imaging studies; a survival analysis was also done.

Results: We found seven (9%) somatic mutations in KRAS and two (2%) in PIK3CA. EGFR mutations were present in 44 (56%). KRAS mutations were found only in tumors without EGFR mutations, whereas PIK3CA mutation was found in tumors with EGFR mutation. Tumor response was assessable in 52 tumors. None of the six tumors with KRAS mutations responded to gefitinib treatment; however, two tumors with PIK3CA mutations showed partial response. Survival was significantly longer in patients with EGFR mutations or in those without KRAS mutations. In tumors with EGFR mutations, survival was longer in those with high PIK3CA or PTEN expression than in those with low expression of these molecules.

Conclusions: An evaluation of the KRAS mutation, as well as PIK3CA and PTEN expression, might help identify lung cancer patients who are most suitable for gefitinib treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents / therapeutic use*
  • Biomarkers, Tumor
  • Class I Phosphatidylinositol 3-Kinases
  • ErbB Receptors / genetics*
  • Female
  • Gefitinib
  • Gene Expression*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / mortality
  • Male
  • Middle Aged
  • Mutation
  • PTEN Phosphohydrolase / genetics*
  • Phosphatidylinositol 3-Kinases / genetics*
  • Protein Kinase Inhibitors / therapeutic use*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Quinazolines / therapeutic use*
  • Survival Rate
  • ras Proteins


  • Antineoplastic Agents
  • Biomarkers, Tumor
  • KRAS protein, human
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • Quinazolines
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • PTEN Phosphohydrolase
  • PTEN protein, human
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Gefitinib