K-ras genotypes and prognosis in non-small-cell lung cancer.
BACKGROUND
Despite major advances in the treatment of many kinds of cancer over the past 25 years, the overall 5-year survival of non-small-cell lung cancer patients has scarcely improved. Even in stage I which has the best outcome long-term survival still falls below 70%. Since intriguing data suggest that the identification of genetic markers might allow prognosis to be assessed case by case. We were prompted to evaluate K-ras gene mutations as a putative prognostic marker in this neoplasm.


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 samples. 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/ASO hybridization were also identified by SSCP. In stage I disease, the median survival was 46 months in those patients whose tumors had no K-ras mutations and 21 months in those with aspartic acid and serine mutations at K-ras codon 12; in patients with stage IIIA disease, median survival time was 16 months in the K-ras negative group and 7 months in the aspartic acid and serine mutation group. No significant differences were observed for the remaining amino acid substitutions of K-ras, nor were they observed at all in more advanced disease.


CONCLUSIONS
K-ras gene status has strong prognostic value in patients with stage 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 non-small-cell lung cancer K-ras genotypic classification should be validated in larger studies.
Rosell
R
R
Medical Oncology Service, University Hospital Germans Trias i Pujol, Badalona, Barcelona, Spain.
Monzo
M
M
Molina
F
F
Martinez
E
E
Pifarre
A
A
Moreno
I
I
Mate
J L
JL
de Anta
J M
JM
Sanchez
M
M
Font
A
A
D000368:Aged; D000483:Alleles; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics*; D005260:Female; D005557:Formaldehyde; D011905:Genes, ras; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D015345:Oligonucleotide Probes; D016612:Paraffin Embedding; D016133:Polymerase Chain Reaction / Q000379:methods*; D018807:Polymorphism, Single-Stranded Conformational; D011379:Prognosis; D012189:Retrospective Studies
D015345:Oligonucleotide Probes; D005557:Formaldehyde