K-RAS GENE-MUTATIONS - AN UNFAVORABLE PROGNOSTIC MARKER IN STAGE-I LUNG ADENOCARCINOMA

Activation of K-ras gene by point mutations, a common finding in lung adenocarcinomas, has been suggested to decrease patient survival. We i nvestigated 109 lung adenocarcinomas, mostly small, peripheral, stage I tumours (81/109) for presence of K-ras gene mutations at codons 12 a nd 13. Mutations were detected by denaturing gradient gel electrophore sis analysis of specific sequences amplified by polymerase chain react ion from DNA extracted from archival pathological material. Thirty-thr ee of 109 (30.3%) tumours showed mutations at codon 12 (28/33, 84.8%) or 13 (5/33, 15.2%) of the gene. Mutations and type of nucleotide subs titutions were differently distributed among cytological subtypes, bei ng more prevalent among less differentiated (G2 and G3) tumours and am ong bronchial than bronchiolo-alveolar type adenocarcinomas. Survival analysis showed an adverse effect of K-ras mutation on survival, restr icted to stage I tumours. Median survival for 81 stage I patients was 30 months for non-mutated tumours versus 20 months for mutated tumours (p = 0.016). Multivariate analysis showed that age of patient (p = 0. 001) and K-ras mutation status (p = 0.04) were the only independent fa ctors influencing survival significantly These data strengthen the hyp othesis that K-ras gene mutations may be useful in identifying a subgr oup of patients with poor outcome.