Somers V A, van Henten A M, ten Velde G P, Arends J W, Thunnissen F B
Dept of Pathology, Maastricht University, The Netherlands.
Eur Respir J. 1999 May;13(5):1120-4. doi: 10.1034/j.1399-3003.1999.13e30.x.
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.
本研究的目的是探讨K-ras点突变在周围型肺肿瘤临床诊断中的附加诊断价值。为此，对支气管镜检查期间从疑似肺癌患者获取的支气管冲洗液进行了研究。仅对那些细胞学诊断不能确诊为恶性肿瘤的患者进行调查。作为对照组，对无肺癌的患者进行了调查。采用“核酸外切酶扩增偶联捕获技术检测点突变”（Point-EXACCT）方法分析支气管冲洗液及相应肿瘤组织（若有）中的K-ras密码子12。在19例未确诊为恶性肿瘤患者的支气管冲洗液中，有4例（21%）检测到K-ras点突变。恶性肿瘤的诊断还基于支气管刷检标本的细胞学检查、经胸针吸活检、活检和切除标本的组织学检查、颈部淋巴结针吸活检及胸水检查。4例K-ras阳性患者中，尽管支气管冲洗液恶性检查结果为阴性，但通过支气管镜检查获得了阳性恶性组织。在肿瘤组织显示K-ras突变的4例患者中，有2例支气管冲洗液K-ras检测呈阳性。对11例无肺癌患者的支气管冲洗液分析未发现K-ras密码子12突变。总之，在支气管镜检查过程中获取的支气管冲洗液中可检测到K-ras点突变。K-ras可作为肺癌临床诊断的生物标志物，在肺癌诊断中可作为细胞学检查的辅助手段。
