J Clin Oncol  1999 Feb;17(2):668-75 

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

Graziano SL, Gamble GP, Newman NB, Abbott LZ, Rooney M, Mookherjee S, Lamb ML,
Kohman LJ, Poiesz BJ.

Department of Medicine, State University of New York Health Science Center and
Veterans Affairs Medical Center, Syracuse 13210, USA.

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 lung cancer
(NSCLC). PATIENTS AND METHODS: We identified 260 patients with surgically
resected stage 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
paraffin-embedded NSCLC tissue, using mutation-specific probes for codon 12
K-ras. RESULTS: K-ras mutations were detected in 35 of 213 assessable specimens
(16.4%). K-ras mutations were detected in 27 of 93 adenocarcinomas (29.0%), one
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 transversions
accounted for 71% of the mutations. There was no statistically significant
difference in overall survival for all patients with K-ras mutations (median
survival, 39 months) compared with patients without K-ras mutations (median
survival, 53 months; P = .33). There was no statistically significant difference
in overall or disease-free survival for subgroups with stage I disease,
adenocarcinoma, or non-squamous cell carcinoma or for specific amino acid
substitutions. The median survival time for stage II patients 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 than in squamous cell carcinomas. For the subgroup with stage II
NSCLC, there was a statistically significant adverse effect on survival for the
presence of K-ras mutations. However, when the entire group was considered, the
presence of K-ras mutations was not of prognostic significance in this cohort of
patients with resected early-stage NSCLC.

PMID: 10080613 [PubMed - indexed for