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Detection and comparison of EGFR mutations in matched tumor tissues, cell blocks, pleural effusions, and sera from patients with NSCLC with malignant pleural effusion, by PNA clamping and direct sequencing.
- Source :
-
Lung cancer (Amsterdam, Netherlands) [Lung Cancer] 2013 Aug; Vol. 81 (2), pp. 207-12. Date of Electronic Publication: 2013 May 29. - Publication Year :
- 2013
-
Abstract
- Peptide nucleic acid (PNA)-mediated real-time PCR clamping has higher sensitivity than conventional direct sequencing for detecting mutations. Pleural effusion and serum may provide good samples in which to detect epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) patients. We studied 37 NSCLC patients with malignant pleural effusion. EGFR mutations were assessed by PNA clamping and direct sequencing using tumor tissues, cell blocks, pleural effusion, and serum. Concordance between PNA clamping and direct sequencing results, and the diagnostic performance of pleural effusion were investigated. The κ coefficients for the two methods were 0.68 (p = 0.0007), 0.91 (p < 0.0001), 0.75 (p < 0.0001) and -0.01 (p = 0.8639) for tissues, cell blocks, pleural effusion, and serum, respectively. The diagnostic performance of pleural effusion compared with the combination of tumor tissue and cell blocks showed 89% sensitivity, 100% specificity, positive predictive value of 100%, and negative predictive value of 95% by PNA clamping, and 67% sensitivity, 90% specificity, positive predictive value of 75%, and negative predictive value of 86% by directing sequencing. A patient in whom an EGFR mutation was identified in pleural effusion only by PNA clamping showed a significant response to EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment. In contrast to the limited role of serum samples, pleural effusion had a diagnostic performance for the detection of EGFR mutations in NSCLC that was comparable to that of tumor tissues and cell blocks. The diagnostic performance of PNA clamping was good compared with that of direct sequencing. A more sensitive and accurate detection of EGFR mutations would benefit patients by allowing a better prediction of the response to EGFR-TKI treatment.<br /> (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Subjects :
- Adult
Aged
Carcinoma, Non-Small-Cell Lung blood
Carcinoma, Non-Small-Cell Lung drug therapy
Carcinoma, Non-Small-Cell Lung enzymology
Female
Humans
Lung Neoplasms blood
Lung Neoplasms drug therapy
Lung Neoplasms enzymology
Male
Middle Aged
Pleural Effusion, Malignant blood
Pleural Effusion, Malignant drug therapy
Pleural Effusion, Malignant enzymology
Protein Kinase Inhibitors pharmacology
Protein-Tyrosine Kinases antagonists & inhibitors
Sequence Analysis, DNA methods
Carcinoma, Non-Small-Cell Lung genetics
ErbB Receptors genetics
Lung Neoplasms genetics
Mutation
Peptide Nucleic Acids genetics
Pleural Effusion, Malignant genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1872-8332
- Volume :
- 81
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Lung cancer (Amsterdam, Netherlands)
- Publication Type :
- Academic Journal
- Accession number :
- 23726527
- Full Text :
- https://doi.org/10.1016/j.lungcan.2013.04.023