K-RAS GENOTYPES AND PROGNOSIS IN NON-SMALL-CELL LUNG-CANCER

Background: Despite major advances in the treatment of many kinds of c ancer over the past 25 years, the overall 5-year survival of non-small -cell lung cancer patients has scarcely improved. Even in stage I whic h has the best outcome long-term survival still falls below 70%. Since intriguing data suggest that the identification of genetic markers mi ght allow prognosis to be assessed case by case. We were prompted to e valuate K-ras gene mutations as a putative prognostic marker in this n eoplasm. Materials and methods: We used the polymerase chain reaction (PCR) followed by allele specific oligonucleotide (ASO) hybridization or single-strand conformation polymorphism (SSCP) assays, to detect K- ras mutations in DNA from formalin-fixed, paraffin-embedded tumor samp les. K-ras mutations were examined in 192 stage I to IV non-small-cell lung cancer patients. Results: K-ras mutations were detected in 51 of 192 of the cases studied (27%). All K-ras mutations detected by PCR/A SO hybridization were also identified by SSCP. In stage I disease, the median survival time was 46 months in those patients whose tumors had no K-ras mutations and 21 months in those with aspartic acid and seri ne mutations at K-ras codon 12; in patients with stage IIIA disease, m edian survival time was 16 months in the K-ras negative group and 7 mo nths in the aspartic acid and serine mutation group. No significant di fferences were observed for the remaining amino acid substitutions of K-ras, nor were they observed at all in more advanced disease. Conclus ions: K-ras gene status has strong prognostic value in patients with s tage IIIA non-small-cell lung cancer. The survival curve for patients with stage I and K-ras codon 12 aspartic or serine mutations is close to that of patients with stage IIIA without K-ras mutations. However, a nonsmall-cell lung cancer K-ras genotypic classification should be v alidated in larger studies.