Prognostic implication of EGFR, KRAS, and TP53 gene mutations in a large cohort of Japanese patients with surgically treated lung adenocarcinoma

J Thorac Oncol. 2009 Jan;4(1):22-9. doi: 10.1097/JTO.0b013e3181914111.


Introduction: Although mutation of the epidermal growth factor receptor (EGFR) gene is predictive for the response to EGFR-tyrosine kinase inhibitor, its prognostic impact for patients without EGFR-tyrosine kinase inhibitor treatment remains controversial. We examined for EGFR, KRAS or TP53 mutations in a consecutive large cohort of patients with lung adenocarcinoma, and evaluated their prognostic impact.

Methods: We analyzed 397 patients with lung adenocarcinoma who underwent potentially curative pulmonary resection. Total ribonucleic acid was extracted and direct sequencing of each gene was performed after reverse transcription-polymerase chain reaction.

Results: We found that 196 patients (49%) had EGFR mutations. Of these, 83 were exon 19 deletions (42%) and 92 were L858R (47%). Univariate analysis showed that patients with EGFR mutations survived for a longer period than those without mutations (p = 0.0046). However, there was no difference in overall survival between the patients with exon 19 deletion and those with L858R (p = 0.4144). Patients with KRAS mutations or TP53 mutations tended to survive for a shorter period (p = 0.2183 and 0.0230, respectively). Multivariate analysis using the Cox proportional hazards model revealed that smoking status (p = 0.0310) and disease stage (p < 0.0001) were independent prognostic factors. However, none of the gene mutations was independent prognostic factors (EGFR, p = 0.3225; KRAS, p = 0.8500; TP53, p = 0.3191).

Conclusions: EGFR, KRAS, and TP53 gene mutations were not independently associated with the prognosis for Japanese patients with surgically treated lung adenocarcinoma.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma / secondary
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Aged, 80 and over
  • Amino Acid Sequence
  • Cell Differentiation
  • Cohort Studies
  • ErbB Receptors / genetics*
  • Female
  • Follow-Up Studies
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Molecular Sequence Data
  • Mutation / genetics*
  • Neoplasm Staging
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • RNA, Neoplasm / genetics
  • RNA, Neoplasm / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Homology, Amino Acid
  • Smoking
  • Survival Rate
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism
  • ras Proteins / genetics*


  • KRAS protein, human
  • Proto-Oncogene Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • EGFR protein, human
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins