Additional value of K-ras point mutations in bronchial wash fluids for diagnosis of peripheral lung tumours.

Dept of Pathology, Maastricht University, The Netherlands.The purpose of this study was to examine the additional diagnostic value of K-ras point mutations in the clinical diagnosis of peripheral lung tumours. To this end, bronchial wash fluids obtained during bronchoscopy from patients suspected of having lung cancer were studied. Only those patients were investigated for whom the cytological diagnosis was not conclusive for malignancy. As a control group, patients without lung cancer were investigated. The method of "point mutation detection using the exonuclease amplification coupled capture technique" (Point-EXACCT) for analysis of K-ras codon 12 was performed in bronchial wash fluids and the corresponding tumour tissue, if available. K-ras point mutations were identified in 4 out of 19 (21%) bronchial wash fluids from patients without a decisive diagnosis of malignancy. The diagnosis of malignancy was further based on cytological examination of bronchial brush specimens, perthoracic needle aspiration, histological investigation of biopsy and resection specimens, needle aspiration of a lymph node in the neck and pleural fluid examination. Four of the patients who were K-ras-positive yielded positive malignant tissue via bronchoscopy even though the bronchial wash was negative for malignancy. The bronchial wash was positive for K-ras in two of the four patients whose tumour tissue demonstrated the K-ras mutations. Analysis of bronchial wash fluids from 11 patients without lung cancer revealed no K-ras codon 12 mutations. In conclusion, K-ras point mutations can be identified in bronchial wash fluids obtained during bronchoscopic procedures. K-ras can be used as a biomarker in the clinical diagnosis of lung cancer and may serve as an adjunct to cytology in lung cancer diagnosis