Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer

Steven A. Ahrendt, John T. Chow, Li Hua Xu, Stephen C. Yang, Claus F. Eisenberger, Manel Esteller, James G. Herman, Li Wu, Anthony Decker, Jin Jen, David Sidransky

Research output: Contribution to journalArticle

297 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)332-339
Number of pages8
JournalJournal of the National Cancer Institute
Volume91
Issue number4
StatePublished - Feb 17 1999
Externally publishedYes

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Bronchoalveolar Lavage Fluid
Lung Neoplasms
Mutation
Non-Small Cell Lung Carcinoma
Neoplasms
Microsatellite Instability
p16 Genes
Polymerase Chain Reaction
CpG Islands
Molecular Pathology
Sputum
Oncogenes
Urinary Bladder Neoplasms
Microsatellite Repeats
Methylation
Ligation
Adenocarcinoma
Alleles
DNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Ahrendt, S. A., Chow, J. T., Xu, L. H., Yang, S. C., Eisenberger, C. F., Esteller, M., ... Sidransky, D. (1999). Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer. Journal of the National Cancer Institute, 91(4), 332-339.

Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer. / Ahrendt, Steven A.; Chow, John T.; Xu, Li Hua; Yang, Stephen C.; Eisenberger, Claus F.; Esteller, Manel; Herman, James G.; Wu, Li; Decker, Anthony; Jen, Jin; Sidransky, David.

In: Journal of the National Cancer Institute, Vol. 91, No. 4, 17.02.1999, p. 332-339.

Research output: Contribution to journalArticle

Ahrendt, SA, Chow, JT, Xu, LH, Yang, SC, Eisenberger, CF, Esteller, M, Herman, JG, Wu, L, Decker, A, Jen, J & Sidransky, D 1999, 'Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer', Journal of the National Cancer Institute, vol. 91, no. 4, pp. 332-339.
Ahrendt SA, Chow JT, Xu LH, Yang SC, Eisenberger CF, Esteller M et al. Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer. Journal of the National Cancer Institute. 1999 Feb 17;91(4):332-339.
Ahrendt, Steven A. ; Chow, John T. ; Xu, Li Hua ; Yang, Stephen C. ; Eisenberger, Claus F. ; Esteller, Manel ; Herman, James G. ; Wu, Li ; Decker, Anthony ; Jen, Jin ; Sidransky, David. / Molecular detection of tumor cells in bronchoalveolar lavage fluid from patients with early stage lung cancer. In: Journal of the National Cancer Institute. 1999 ; Vol. 91, No. 4. pp. 332-339.
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abstract = "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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AU - Ahrendt, Steven A.

AU - Chow, John T.

AU - Xu, Li Hua

AU - Yang, Stephen C.

AU - Eisenberger, Claus F.

AU - Esteller, Manel

AU - Herman, James G.

AU - Wu, Li

AU - Decker, Anthony

AU - Jen, Jin

AU - Sidransky, David

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N2 - 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.

AB - 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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