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

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.