Impact of KRAS and EGFR gene mutations on recurrence and survival in patients with surgically resected lung adenocarcinomas

Ann Surg Oncol. 2012 Jul:19 Suppl 3:S347-54. doi: 10.1245/s10434-011-1799-8. Epub 2011 May 24.

Abstract

Background: Oncogenic gene mutations observed in lung adenocarcinomas, such as epidermal growth factor receptor (EGFR) and KRAS, have some predictive value for chemotherapeutic drugs or EGFR-tyrosine kinase inhibitors. However, the influence of these gene alterations on patients' prognosis remains controversial.

Methods: We retrospectively analyzed the tumors of 180 patients with completely resected pathological stage I-III lung adenocarcinoma which harbored either KRAS codon 12 mutation or EGFR gene mutations within exons 18-21 to investigate the impact of these gene mutations on the patients' survival. Gene mutations were detected by established methods.

Results: Of 180 patients, 32 had KRAS codon 12 mutations (KRAS group), 148 had EGFR mutations within exon 18-21 (EGFR group). Pathological stage and operation mode were independent factors for disease-free survival. However, the EGFR group had better overall survival than the KRAS group (P = 0.0271). Cox proportional hazard model revealed pathological stage (P = 0.0001) and presence of EGFR gene mutations (P = 0.0408) were independent factors for overall survival. In survival after tumor recurrence, the EGFR group had a better median survival time (46.7 months) after recurrence than the KRAS group (26.0 months).

Conclusions: In patients with completely resected lung adenocarcinomas, KRAS and EGFR gene mutation status of tumors was not associated with disease-free survival. However, the presence of an EGFR gene mutation boded well for the patient's overall survival, and thus patients with EGFR mutations have a better prognosis than those with KRAS mutations.

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Codon
  • Disease-Free Survival
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics*
  • Exons
  • Female
  • Genes, Neoplasm
  • Humans
  • Kaplan-Meier Estimate
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Mutagenesis, Insertional
  • Neoplasm Recurrence, Local / drug therapy
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / therapy
  • Point Mutation
  • Proportional Hazards Models
  • Protein Kinase Inhibitors / administration & dosage
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Retrospective Studies
  • Sequence Deletion
  • Time Factors
  • ras Proteins / genetics*

Substances

  • Codon
  • KRAS protein, human
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins