Miep A van der Drift1, Clemens F M Prinsen2, G Jimmy Knuiman2, Julius P Janssen3, P N Richard Dekhuijzen4, Frederic B J M Thunnissen2. 1. Department of Pulmonary Diseases, Radboud University Nijmegen Medical Centre, Nijmegen The Netherlands. Electronic address: m.vanderdrift@uccz.umcn.nl. 2. Departments of Pathology, Nijmegen, The Netherlands. 3. Departments of Pulmonary Diseases, Canisius-Wilhelmina Hospital, Nijmegen, The Netherlands. 4. Department of Pulmonary Diseases, Radboud University Nijmegen Medical Centre, Nijmegen The Netherlands.
Abstract
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.
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 ratsarcoma 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 cancerpatients 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.
Authors: Victoria Sarne; Samuel Huter; Sandrina Braunmueller; Lisa Rakob; Nico Jacobi; Melitta Kitzwögerer; Christoph Wiesner; Peter Obrist; Rita Seeboeck Journal: Int J Mol Sci Date: 2020-06-28 Impact factor: 5.923
Authors: Georgios Nikolaidis; Olaide Y Raji; Soultana Markopoulou; John R Gosney; Julie Bryan; Chris Warburton; Martin Walshaw; John Sheard; John K Field; Triantafillos Liloglou Journal: Cancer Res Date: 2012-09-07 Impact factor: 12.701