Originally published as JCO Early Release 10.1200/JCO.2003.02.006 on September 24 2003

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Quantification of Free Circulating DNA As a Diagnostic Marker in Lung Cancer

Gabriella Sozzi, Davide Conte, MariaElena Leon, Rosalia Cirincione, Luca Roz, Cathy Ratcliffe, Elena Roz, Nicola Cirenei, Massimo Bellomi, Giuseppe Pelosi, Marco A. Pierotti, Ugo Pastorino

From the Departments of Experimental Oncology and Thoracic Surgery, Istituto Nazionale Tumori; Divisions of Thoracic Surgery, Anatomical Pathology, Radiology, and Epidemiology, European Institute of Oncology, Milan; and Applera Italia, Monza, Italy.

Address reprint requests to Ugo Pastorino, MD, Department of Thoracic Surgery, Istituto Nazionale Tumori, Via Venezian 1, 20133 Milan, Italy; e-mail: ugo.pastorino{at}istitutotumori.mi.it.

Purpose: Analysis of circulating DNA in plasma can provide a useful marker for earlier lung cancer detection. This study was designed to assess the sensitivity and specificity of a quantitative molecular assay of circulating DNA to identify patients with lung cancer and monitor their disease.

Materials and Methods: The amount of plasma DNA was determined through the use of real-time quantitative polymerase chain reaction (PCR) amplification of the human telomerase reverse transcriptase gene (hTERT) in 100 non–small-cell lung cancer patients and 100 age-, sex-, and smoking-matched controls. Screening performance of the assay was calculated through the receiver operating characteristic (ROC) curve. Odds ratios were calculated using conditional logistic regression analysis.

Results: Median concentration of circulating plasma DNA in patients was almost eight times the value detected incontrols (24.3 v 3.1 ng/mL). The area under the ROC curve was 0.94 (95% CI, 0.907 to 0.973). Plasma DNA was a strong risk factor for lung cancer; concentrations in the upper tertile were associated with an 85-fold higher risk than were those in the lowest tertile.

Conclusion: This study shows that higher levels of free circulating DNA can be detected in patients with lung cancer compared with disease-free heavy smokers by a PCR assay, and suggests a new, noninvasive approach for early detection of lung cancer. Levels of plasma DNA could also identify higher-risk individuals for lung cancer screening and chemoprevention trials.

Supported by a Research Grant from the Italian Ministry of Health (Ricerca Finalizzata) and the Italian Association for Cancer Research (AIRC/FIRC).

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• Free Circulating DNA: Good As a Diagnostic Marker in Lung Cancer?
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