Diagnosing peripheral lung cancer: the additional value of the Ras-association domain family 1A gene methylation and Kirsten rat sarcoma 2 viral oncogene homolog mutation analyses in washings in nondiagnostic bronchoscopy.
Publication year
2012Source
Chest, 141, 1, (2012), pp. 169-175ISSN
Annotation
1 januari 2012
Publication type
Article / Letter to editor

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Organization
Pulmonary Diseases
Biochemistry (UMC)
Journal title
Chest
Volume
vol. 141
Issue
iss. 1
Page start
p. 169
Page end
p. 175
Subject
N4i 1: Pathogenesis and modulation of inflammation; N4i 3: Poverty-related infectious diseases ONCOL 5: Aetiology, screening and detectionAbstract
BACKGROUND: The diagnostic yield of bronchoscopy in patients with endoscopically nonvisible (peripheral) tumors varies from 40% to 56%. Increasingly, molecular markers in bronchial washings are being investigated to improve the diagnostic yield. The aim of this study was to analyze the diagnostic value of the Ras association domain family 1A gene (RASSF1A) methylation analysis in washings in nondiagnostic bronchoscopy in the analysis of patients with suspected lung cancer who had peripheral tumors. Furthermore, the additional diagnostic value of Kirsten rat sarcoma 2 viral oncogene homolog (KRAS) mutations with RASSF1 methylation was analyzed. METHODS: From a prospectively collected series, 129 patients with lung cancer and 28 control subjects were analyzed retrospectively regarding the methylation status of the promoter region of the RASSF1A gene by quantitative methylation-specific polymerase chain reaction and KRAS point mutations by using the sensitive Point-EXACCT method. RESULTS: A total of 40% of the lung cancer patients had peripheral tumors, and 17 patients had a nondiagnostic bronchoscopy. In these patients, RASSF1A methylation was detected in the washings of four patients (24%), and KRAS mutations were detected in the washings of two patients (12%). In total, 29% of the false-negative or doubtful cytology results were accompanied by RASSF1A methylation or KRAS mutation results that were highly suggestive of malignancy. The proportion of RASSF1A methylation was significantly higher in central and larger tumors. No relevant RASSF1A methylation was detected in control samples. CONCLUSIONS: Our data suggest that the molecular analysis of two biomarkers in nondiagnostic bronchial washings may better guide diagnostic procedures in patients with suspected lung cancer.
This item appears in the following Collection(s)
- Academic publications [204996]
- Faculty of Medical Sciences [81051]
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