Skip Navigation LinksHome > August 2007 - Volume 2 - Issue 8 > Sputum Methylation Analysis Detects Patients With Lung Cance...
Journal of Thoracic Oncology:
doi: 10.1097/01.JTO.0000283166.73610.9d
Profferred Paper Abstracts: Session B4: Prevention & Early Detection: + Epidemiology: Tuesday, September 4: Prevention & Early Detection + Epidemiology, Tue, 13:45 - 15:30

Sputum Methylation Analysis Detects Patients With Lung Cancer: B4-07

Thunnissen, Erik1; Shivapurkar, Narayan2; Stastny, Victor2; Drift, Miep v.3; Bolijn, Anne4; Hol, Bernard5; Yinghui, Wang6; Feng, Ziding6; Gazdar, Adi2; Prinsen, Clemens4

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1 VUMC Pathology, Amsterdam, The Netherlands 2 Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX, USA 3 UMCN Pulmonology, Nijmegen, The Netherlands 4 CWZ Pathology, Nijmegen, The Netherlands 5 CWZ Pulmonology, Nijmegen, The Netherlands 6 Fred Hutchinson Cancer Research Center, Seattle, WA, USA

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Sputum methylation analysis is feasible and by some studies suggested to show an increased risk for lung cancer. The aim of this study was to examine 6 methylation markers in sputum of patients with lung cancer and controls.

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In the Canisius Wilhelmina Hospital Nijmegen sputum has been prospectively collected for several years of patients with lung cancer and controls. From this bank 102 cases with lung cancer and 102 controls, most of them with COPD DNA was retrospectively extracted. Samples were subsequently randomized and blinded (TdB). Coded samples were exchanged between collaborators unaware of its origin. Quantitative MSP was performed for APC, Cytoglobin, MGMT, 3-OST-2, p16, RASSF1A, and TCF21. Follow-up was retrieved independently (MvdD). Pathology diagnosis was based on biopsy or only cytology. After submission of methylation data (to ZF with subsequent information of TdB) statistical analysis was performed (WY,ZF).

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The pathology diagnosis was squamous cell carcinoma (n=23), adenocarcinoma (n=23), SCLC (n=16) or NSCLC not further specified. The 77 of the 102 controls had a Gold score for COPD >0. Sputum samples were collected within 6 months of lung cancer diagnosis. Follow-up of COPD cases was minimally 2 years.

Reproducibility of methylation analysis between two labs was poor for MGMT.

RASSF1A showed hypermethylation in 81 % of the SCLC and 69% of the NSCLC lung cancer cases with a specificity of 94 and 74%, respectively. For two markers the sensitivity showed a decrease in sensitivity for SCLC and NSCLC to 50%, and 57%, respectively. The specificity increased for SCLC and NSCLC to 99 and 95%, respectively.

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This blinded study shows that hypermethylation in sputum is with two markers detects 50% of the lung cancer patients.

Copyright © 2007 by the European Lung Cancer Conference and the International Association for the Study of Lung Cancer.


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