Is there a prognostic role of K-ras point mutations in the serum of patients with advanced non-small cell lung cancer?
The purpose of this study was to investigate the prognostic significance of K-ras mutations in circulating DNA in advanced non-small lung cancer (NSCLC) patients. Serum samples were assessed prior to platinum-based chemotherapy start in 67 patients with advanced NSCLC (stage IIIB or IV), treated between April 1999 and June 2002. Patients were not previously treated with chemotherapy. K-ras oncogene mutations at codon 12 were analyzed by genomic amplification and direct sequencing of the patient's DNA present in serum. Pre-treatment serum was available in all 67 patients. Twenty patients (30%) demonstrated K-ras mutations while 47 patients (70%) had wild-type K-ras. Among K-ras mutations, the amino acid glycine was substituted by cystein in 90% and valine in 10%. When patients were grouped according to K-ras genotype, there was no significant difference for any of the baseline patient characteristics. There was a tendency towards a higher response rate for patients with K-ras mutations versus wild-type K-ras in serum, however not statistically significant (p=0.37). Median progression-free survival was 7.3 months versus 5.5 months in patients with mutations and with wild-type K-ras, respectively (p=0.23). For median overall survival time, the mutation group was comparable to the wild-type K-ras group with 12.5 and 11.4 months, respectively (p=0.28). In conclusion, there were no significant differences between the patients with K-ras mutations and those with wild-type genotype with respect to baseline patient characteristics, response rates, progression-free survival, or overall survival.
Camps
Carlos
C
Servicio de Oncología Médica, Hospital General Universitario de Valencia, Av. Tres Cruces s/n, 46014 Valencia, Spain. camps_car@gva.es
Sirera
Rafael
R
Bremnes
Roy
R
Blasco
Ana
A
Sancho
Eva
E
Bayo
Pilar
P
Safont
Maria Jose
MJ
Sánchez
José Javier
JJ
Tarón
Miquel
M
Rosell
Rafael
R
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D003062:Codon; D004273:DNA, Neoplasm / Q000097:blood / Q000235:genetics; D003627:Data Interpretation, Statistical; D005260:Female; D005784:Gene Amplification; D011905:Genes, ras; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D017354:Point Mutation; D011379:Prognosis; D012680:Sensitivity and Specificity; D016019:Survival Analysis
D003062:Codon; D004273:DNA, Neoplasm