Correlation between K-ras gene mutation and prognosis of patients with nonsmall cell lung carcinoma

Cancer. 1997 Feb 1;79(3):462-7. doi: 10.1002/(sici)1097-0142(19970201)79:3<462::aid-cncr6>;2-k.


Background: Mutations at codons 12, 13, and 61 of the three ras genes, H-ras, K-ras, and N-ras, convert these genes into active oncogenes. It appears that ras gene mutations can be found in a variety of tumor types. The purpose of this study was to evaluate the clinical significance of K-ras gene mutation in nonsmall cell lung carcinoma (NSCLC).

Methods: The authors analyzed 58 NSCLC patients for mutations at codons 12, 13, and 61 of the K-ras gene and correlated the findings with the tumor stage and patient survival. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and the direct nucleotide sequencing method were used to detect mutations after amplification of ras specific sequences by PCR.

Results: Fourteen mutations (24%) of ras genes were found, all at codon 12 of the K-ras gene. GGT to GAT transition was the predominant mutational pattern. There was a significant association between K-ras mutation and the tumor stage (i.e., the higher the stage, the higher the mutation rate) (P = 0.014). Using univariate analysis, the presence of K-ras mutation in paraffin embedded tissue from patients who received treatment with curative intent was associated with a shorter survival (P = 0.039). The median survival duration for patients with or without K-ras mutation was 9 and 30 months, respectively. The Cox proportional hazards model also predicted a higher risk for patients with K-ras mutations (P = 0.047).

Conclusions: K-ras mutations, present in a subset of NSCLC, are associated with tumor progression and shortened patient survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • DNA Probes
  • Disease Progression
  • Female
  • Genes, ras / genetics*
  • Humans
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Prognosis
  • Survival Analysis


  • DNA Probes