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Genetic Deletions in Sputum as Diagnostic Markers for Early Detection of Stage I Non–Small Cell Lung Cancer

Authors' Affiliations: Departments of ¹ Surgery, ² Medicine, and ³ Pathology, The University of Maryland School of Medicine; ⁴ Division of Biostatistics, The University of Maryland Greenebaum Cancer Center, Baltimore, Maryland; and ⁵ Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas

Requests for reprints: Feng Jiang, Department of Pathology, The University of Maryland School of Medicine, 10 South Pine Street, MSTF 7th Floor, Baltimore, MD 21201-1192. Phone: 410-706-7056; Fax: 410-706-8414; E-mail: fjiang{at}som.umaryland.edu.

Purpose: Analysis of molecular genetic markers in biological fluids has been proposed as a powerful tool for cancer diagnosis. We have characterized in detail the genetic signatures in primary non–small cell lung cancer, which provided potential diagnostic biomarkers for lung cancer. The aim of this study was to determine whether the genetic changes can be used as markers in sputum specimen for the early detection of lung cancer.

Experimental Design: Genetic aberrations in the genes HYAL2, FHIT, and SFTPC were evaluated in paired tumors and sputum samples from 38 patients with stage I non–small cell lung cancer and in sputum samples from 36 cancer-free smokers and 28 healthy nonsmokers by using fluorescence in situ hybridization.

Results: HYAL2 and FHIT were deleted in 84% and 79% tumors and in 45% and 40% paired sputum, respectively. SFTPC was deleted exclusively in tumor tissues (71%). There was concordance of HYAL2 or FHIT deletions in matched sputum and tumor tissues from lung cancer patients (r = 0.82, P = 0.04; r = 0.84, P = 0.03), suggesting that the genetic changes in sputum might indicate the presence of the same genetic aberrations in lung tumors. Furthermore, abnormal cells were found in 76% sputum by detecting combined HYAL2 and FHIT deletions whereas in 47% sputum by cytology, of the cancer cases, implying that detecting the combination of HYAL2 and FHIT deletions had higher sensitivity than that of sputum cytology for lung cancer diagnosis. In addition, HYAL2 and FHIT deletions in sputum were associated with smoking history of cancer patients and smokers (both P < 0.05).

Conclusions: Tobacco-related HYAL2 and FHIT deletions in sputum may constitute diagnostic markers for early-stage lung cancer.

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