Prognostic significance of K-ras codon 12 mutations in patients with resected stage I and II non-small-cell lung cancer

Purpose: The aim of this study was to investigate the prognostic importance of codon 12 K-ras mutations in patients with early-stage non-small-cell lu ng cancer (NSCLC). Patients and Methods: We identified 260 patients with surgically resected s tage I (n = 193) and stage II (n = 67) NSCLC with at least a 5-year follow- up. We performed polymerase chain reaction analysis of DNA obtained from pa raffin-embedded NSCLC tissue, using mutation-specific probes for codon 12 K -ras, Results: K-ras mutations were detected in 35 of 213 assessable specimens (1 6.4%). K-ras mutations were detected in 27 of 93 adenocarcinomas (29.0%), o ne of 61 squamous cell carcinomas (1.6%), five of 39 large-cell carcinomas (12.8%), and two of 20 adenosquamous carcinomas (10%) (P =.001). G to T tra nsversions accounted for 71% of the mutations. There was no statistically s ignificant difference in overall survival for all patients with K-ros mutat ions (median survival, 39 months) compared with patients without K-ras muta tions (median survival, 53 months; P =.33). There was no statistically sign ificant difference in overall or disease-free survival for subgroups with s tage I disease, adenocarcinoma, or non-squamous cell carcinoma or for speci fic amino acid substitutions, The median survival rime for stage II patient s with K-ras mutations was 13 months, compared with 38 months for patients without K-ras mutations (P =.03). Conclusion: Codon 12 K-ras mutations were more common in adenocarcinomas th an in squamous cell carcinomas. For the subgroup with stage II NSCLC, there was a statistically significant adverse effect on survival for the presenc e of K-ras mutations. However, when the entire group was considered, the pr esence of K-ras mutations was not of prognostic significance in this cohort of patients with resected early-stage NSCLC. (C) 1999 by American Society of Clinical Oncology.