Is there a prognostic role of K-ras point mutations in the serum of patients with advanced non-small cell lung cancer?

• Published in: Lung cancer (Amsterdam, Netherlands) Vol. 50; no. 3; pp. 339 - 346
• Main Authors: Camps, Carlos, Sirera, Rafael, Bremnes, Roy, Blasco, Ana, Sancho, Eva, Bayo, Pilar, Safont, Maria Jose, Sánchez, José Javier, Tarón, Miquel, Rosell, Rafael
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier Ireland Ltd 01.12.2005; Elsevier Science
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; Carcinoma, Non-Small-Cell Lung - blood; Carcinoma, Non-Small-Cell Lung - diagnosis; Carcinoma, Non-Small-Cell Lung - genetics; Codon; Data Interpretation, Statistical; DNA, Neoplasm - blood; DNA, Neoplasm - genetics; Female; Gene Amplification; Genes, ras; Genotype; Humans; K-ras; Lung Neoplasms - blood; Lung Neoplasms - diagnosis; Lung Neoplasms - genetics; Male; Medical sciences; Middle Aged; Molecular markers; Non-small cell lung cancer; NSCLC; Pneumology; Point Mutation; Prognosis; Prognostic factors; Sensitivity and Specificity; Survival Analysis; Tumors of the respiratory system and mediastinum; Molecular markers; NSCLC; K-ras; Prognostic factors; Non-small cell lung cancer; Human; Lung disease; Prognosis; Respiratory disease; Lung cancer; Non-small celt lung cancer; Malignant tumor; Molecular marker; non-small cell lung carcinoma; Point mutation; Bronchus disease; Serum; Onc gene; Non small cell carcinoma
• ISSN: 0169-5002; 1872-8332
• DOI: 10.1016/j.lungcan.2005.06.007

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.