DETECTION OF K-RAS POINT MUTATIONS IN SPUTUM FROM PATIENTS WITH ADENOCARCINOMA OF THE LUNG BY POINT-EXACCT

Purpose: Kirsten ras (K-ras) point mutations are found in 30% to 56% o f pulmonary adenocarcinomas by means of highly sensitive techniques. R ecently, the point-EXACCT (paint mutation detection using exonuclease amplification coupled capture technique) method was described, which d etected one cell with a mutation in 15,000 normal cells. The aim of th is study was to examine whether K-ras point mutations could be found w ith this rapid method in the sputum of patients with adenocarcinoma of the lung. Patients and Methods: DNA from paraffin-embedded-adenocarci noma and corresponding sputum samples were analyzed for mutations of t he K-ras gene. Twenty-eight biopsy specimens and 54 sputum samples of 22 patients were used for amplification and K-ras codon 12 point mutat ion detection. Results: In 11 of 22 patients (50%), a mutation in K-ra s codon 12 was shown in the tumor sample. In five of 11 patients (45%) with a K-ras mutation in the tumor, the same type of mutation was ide ntified in at least one sputum sample. A mutation could not be detecte d in any of the sputum samples from patients with a K-ras-negative tum or. Time between K-ras point mutation detection in sputum and clinical diagnosis of lung cancer varied from 1 month to almost 4 years. In tw o of the five patients with K-ras-positive sputum specimens, malignant cells were found with cytologic examination. Conclusion: point-EXACCT is suitable for the detection of K-ras point mutations in sputum samp les of patients with adenocarcinoma of the lung. This approach may be an important adjunct to cytology in the early diagnosis of lung cancer . J Clin Oncol 16:3061-3068. (C) 1998 by American Society of Clinical Oncology.