© 1999 by Oxford University Press
Journal of the National Cancer Institute, Vol. 91, No. 4, 332-339,
February 17, 1999
© 1999 Oxford University Press
ARTICLES |
Molecular Detection of Tumor Cells in Bronchoalveolar Lavage Fluid From Patients With Early Stage Lung Cancer
Affiliations of authors: S. A. Ahrendt, P. A. Decker,Department of Surgery, Medical College of Wisconsin, Milwaukee; J. T. Chow, L.-H. Xu, C. F. Eisenberger, L. Wu, J. Jen, D. Sidransky (Department of Otolaryngology-Head and Neck Surgery), S. C. Yang (Department of Surgery), M. Esteller, J. G. Herman (The Oncology Center), The Johns Hopkins School of Medicine, Baltimore, MD.
Correspondence to: David Sidransky, M.D., Department of Otolaryngology-Head and Neck Surgery, The Johns Hopkins School of Medicine, 720 Rutland Ave., Baltimore, MD 21205-2196 (e-mail: dsidrans{at}welchlink.welch.jhu.edu).
BACKGROUND: Conventional cytologic analysis of sputum is an insensitive test for the diagnosis of non-small-cell lung cancer (NSCLC). We have recently demonstrated that polymerase chain reaction (PCR)-based molecular methods are more sensitive than cytologic analysis in diagnosing bladder cancer. In this study, we examined whether molecular assays could identify cancer cells in bronchoalveolar lavage (BAL) fluid. METHODS: Tumor-specific oncogene mutations, CpG-island methylation status, and microsatellite alterations in the DNA of cells in BAL fluid from 50 consecutive patients with resectable (stages I through IIIa) NSCLC were assessed by use of four PCR-based techniques. RESULTS: Of 50 tumors, 28 contained a p53 mutation, and the identical mutation was detected with a plaque hybridization assay in the BAL fluid of 39% (11 of 28) of the corresponding patients. Eight of 19 adenocarcinomas contained a K-ras mutation, and the identical mutation was detected with a mutation ligation assay in the BAL fluid of 50% (four of eight) of the corresponding patients. The p16 gene was methylated in 19 of 50 tumors, and methylated p16 alleles were detected in the BAL fluid of 63% (12 of 19) of the corresponding patients. Microsatellite instability in at least one marker was detected with a panel of 15 markers frequently altered in NSCLC in 23 of 50 tumors; the identical alteration was detected in the BAL fluid of 14% (three of 22) of the corresponding patients. When all four techniques were used, mutations or microsatellite instability was detected in the paired BAL fluid of 23 (53%) of the 43 patients with tumors carrying a genetic alteration. CONCLUSION: Although still limited by sensitivity, molecular diagnostic strategies can detect the presence of neoplastic cells in the proximal airway of patients with surgically resectable NSCLC.
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G. Ferretti, G. Curigliano, U. Pastorino, A. Cittadini, G. Flamini, M. G. Calabrò, Tommaso De Pas, L. Orlando, M. Mandalà, M. Colleoni, et al. Detection by Denaturant Gradient Gel Electrophoresis of Tumor-specific Mutations in Biopsies and Relative Bronchoalveolar Lavage Fluid from Resectable Non-Small Cell Lung Cancer Clin. Cancer Res., June 1, 2000; 6(6): 2393 - 2400. [Abstract] [Full Text]
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M. Sanchez-Cespedes, M. Esteller, L. Wu, H. Nawroz-Danish, G. H. Yoo, W. M. Koch, J. Jen, J. G. Herman, and D. Sidransky Gene Promoter Hypermethylation in Tumors and Serum of Head and Neck Cancer Patients Cancer Res., February 1, 2000; 60(4): 892 - 895. [Abstract] [Full Text]
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K. M. Fong, Y. Sekido, and J. D. Minna MOLECULAR PATHOGENESIS OF LUNG CANCER J. Thorac. Cardiovasc. Surg., December 1, 1999; 118(6): 1136 - 1152. [Abstract] [Full Text] [PDF]
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X. q. Chen, H. Bonnefoi, S. Diebold-Berger, J. Lyautey, C. Lederrey, E. Faltin-Traub, M. Stroun, and P. Anker Detecting Tumor-related Alterations in Plasma or Serum DNA of Patients Diagnosed with Breast Cancer Clin. Cancer Res., September 1, 1999; 5(9): 2297 - 2303. [Abstract] [Full Text] [PDF]
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M. Sanchez-Cespedes, M. Esteller, K. Hibi, F. O. Cope, W. H. Westra, S. Piantadosi, J. G. Herman, J. Jen, and D. Sidransky Molecular Detection of Neoplastic Cells in Lymph Nodes of Metastatic Colorectal Cancer Patients Predicts Recurrence Clin. Cancer Res., September 1, 1999; 5(9): 2450 - 2454. [Abstract] [Full Text] [PDF]
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M. Takahama, M. Tsutsumi, T. Tsujiuchi, K. Nezu, K. Kushibe, S. Taniguchi, Y. Kotake, and Y. Konishi Enhanced Expression of Tie2, Its Ligand Angiopoietin-1, Vascular Endothelial Growth Factor, and CD31 in Human Non-Small Cell Lung Carcinomas Clin. Cancer Res., September 1, 1999; 5(9): 2506 - 2510. [Abstract] [Full Text] [PDF]
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Y. M. D. Lo, I. H. N. Wong, J. Zhang, M. S. C. Tein, M. H. L. Ng, and N. M. Hjelm Quantitative Analysis of Aberrant p16 Methylation Using Real-Time Quantitative Methylation-specific Polymerase Chain Reaction Cancer Res., August 1, 1999; 59(16): 3899 - 3903. [Abstract] [Full Text] [PDF]
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A. F. Gazdar and J. D. Minna Molecular Detection of Early Lung Cancer J Natl Cancer Inst, February 17, 1999; 91(4): 299 - 301. [Full Text] [PDF]
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