Startseite Predicting outcomes of EGFR-targeted therapy in non-small cell lung cancer patients using pleural effusions samples and peptide nucleic acid probe assay
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Predicting outcomes of EGFR-targeted therapy in non-small cell lung cancer patients using pleural effusions samples and peptide nucleic acid probe assay

  • Mei-Chia Wang , Chih-Liang Wang , Tai-Long Chen , John Wen-Cheng Chang , Jang-Jih Lu , Pi-Yueh Chang EMAIL logo und Chiuan-Chian Chiou EMAIL logo
Veröffentlicht/Copyright: 8. August 2017
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Clinical Chemistry and Laboratory Medicine (CCLM)
Aus der Zeitschrift Clinical Chemistry and Laboratory Medicine (CCLM) Band 55 Heft 12

Abstract

Background:

Mutation of epidermal growth factor receptor (EGFR) is a prediction marker of the response to tyrosine kinase inhibitor (TKI) drugs in non-small cell lung cancer (NSCLC) patients. As late stage lung cancer patients rarely undergo surgery, samples for EGFR mutation identification usually come from computed tomography (CT)-guided or endoscopic biopsies, which is invasive and costly. Pleural effusion may serve as a less invasive sample for EGFR mutation detection.

Methods:

We designed a fluorophore-labeled peptide nucleic acid (PNA) probe assay for three types of EGFR mutations, including exon 19 deletions, L858R point mutations and T790M point mutations. The assay was applied in 39 pleural effusion samples from NSCLC patients. The correlation between detected EGFR status and clinical outcome were analyzed.

Results:

In 15 paired samples, PNA probe assay in pleural effusion samples could detect all the mutations that were identified by conventional PCR plus Sanger sequencing in tissue biopsies. In addition, PNA probe assay detected three more T790M mutations. In all 39 pleural effusions, the PNA probe assay detected 27 having at least one of the three EGFR mutations. Among the patients before TKI treatment, those with a sensitizing mutation (either exon 19 deletion or L858R) but without T790M, had 94.1% response rate and longer progression-free survival (mean 10.8 months) than patients without detected mutation (mean 4.2 months) and patients with T790M (mean 1.7 months).

Conclusions:

Mutations detected in pleural effusions using PNA probe assay are highly associated with clinical outcome. This method appears to be a reliable way for the prediction of the efficacy of EGFR-targeted therapy.

Keywords: epidermal growth factor receptor mutation; non-small cell lung cancer; peptide nucleic acid probe; pleural effusion; tyrosine kinase inhibitor
Corresponding authors: Pi-Yueh Chang, PhD, Department of Laboratory Medicine, Chang-Gung Memorial Hospital, Taoyuan, Taiwan; and Chiuan-Chian Chiou, PhD, Department of Medical Biotechnology and Laboratory Science, Chang Gung University, Taoyuan, Taiwan
aMei-Chia Wang and Chih-Liang Wang contributed equally to this work.

Acknowledgments

We thank professor Hsin-Chih Lai and Alexander J. Boyd for the comments and suggestions on the manuscript structure and language editing.

  1. Author contributions: Conception and designation: MW CW JL PC CC. Perform the experiment: MW CW TC WC. Data collection and analysis: MW CW TC WC. Wrote the paper: MW TC PC CC.

  2. Research funding: This study was supported by Chang Gung Memorial Hospital (CMRPG391891), Taiwan.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Supplemental Material:

The online version of this article (https://doi.org/10.1515/cclm-2016-0809) offers supplementary material, available to authorized users.

Received: 2016-9-8
Accepted: 2017-5-17
Published Online: 2017-8-8
Published in Print: 2017-10-26

©2017 Walter de Gruyter GmbH, Berlin/Boston

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Tumor microenvironment and systemic disease: a dual target in medical oncology (also in the case of biomarkers)
  4. Reviews
  5. Sample types applied for molecular diagnosis of therapeutic management of advanced non-small cell lung cancer in the precision medicine
  6. The impact of pneumatic tube system on routine laboratory parameters: a systematic review and meta-analysis
  7. Opinion Paper
  8. How to reduce scientific irreproducibility: the 5-year reflection
  9. EFLM Paper
  10. Strategies to define performance specifications in laboratory medicine: 3 years on from the Milan Strategic Conference
  11. General Clinical Chemistry and Laboratory Medicine
  12. Intensive educational efforts combined with external quality assessment improve the preanalytical phase in general practitioner offices and nursing homes
  13. Separate patient serum sodium medians from males and females provide independent information on analytical bias
  14. Are admission procalcitonin levels universal mortality predictors across different medical emergency patient populations? Results from the multi-national, prospective, observational TRIAGE study
  15. Biochemical testing in a laboratory tent and semi-intensive care of Ebola patients on-site in a remote part of Guinea: a paradigm shift based on a bleach-sensitive point-of-care device
  16. Efficient reporting of the estimated glomerular filtration rate without height in pediatric patients with cancer
  17. Evaluation of thyroid test utilization through analysis of population-level data
  18. Relation of serum γ-glutamyl transferase activity with copper in an adult population
  19. Impact of a single oral dose of 100,000 IU vitamin D3 on profiles of serum 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 in adults with vitamin D insufficiency
  20. Automated antinuclear immunofluorescence antibody analysis is a reliable approach in routine clinical laboratories
  21. Infrared analyzers for breast milk analysis: fat levels can influence the accuracy of protein measurements
  22. Hematology and Coagulation
  23. A new approach to define acceptance limits for hematology in external quality assessment schemes
  24. The effects of transport by car on coagulation tests
  25. Combined measurement of factor XIII and D-dimer is helpful for differential diagnosis in patients with suspected pulmonary embolism
  26. Reference Values and Biological Variations
  27. Influence of age, gender and body mass index on late-night salivary cortisol in healthy adults
  28. Cancer Diagnostics
  29. Assessment of real-time PCR method for detection of EGFR mutation using both supernatant and cell pellet of malignant pleural effusion samples from non-small-cell lung cancer patients
  30. Detection of EGFR mutations in patients with non-small cell lung cancer by high resolution melting. Comparison with other methods
  31. Predicting outcomes of EGFR-targeted therapy in non-small cell lung cancer patients using pleural effusions samples and peptide nucleic acid probe assay
  32. Analytical and clinical performance of thyroglobulin autoantibody assays in thyroid cancer follow-up
  33. Thyroglobulin autoantibodies before radioiodine ablation predict differentiated thyroid cancer outcome
  34. Cardiovascular Diseases
  35. Real life dabigatran and metabolite concentrations, focused on inter-patient variability and assay differences in patients with atrial fibrillation
  36. Infectious Diseases
  37. HIV avidity index performance using a modified fourth-generation immunoassay to detect recent HIV infections
  38. Letters to the Editor
  39. Effect of age on serum prostate-specific antigen in women
  40. Falsely elevated thyroid-stimulating hormone value due to anti-ruthenium antibodies in a patient with primary hypothyroidism: a case report
  41. High titers of anti-infliximab antibody do not interfere with Abbott immunoassays
  42. Extraordinarily elevated serum CA19-9 in a patient with posterior mediastinum cyst: a case report
  43. Low levels of 25-OH vitamin D in women with endometriosis and associated pelvic pain
  44. Evaluation of serum cortisol biological variation in the evening withdrawal
  45. Distinction between urine crystals by automated urine analyzer SediMAX conTRUST is specific but lacks sensitivity
  46. Impact of heat-inactivation on anti-Toxoplasma IgM antibody levels
https://doi.org/10.1515/cclm-2016-0809
Schlagwörter für diesen Artikel
epidermal growth factor receptor mutation; non-small cell lung cancer; peptide nucleic acid probe; pleural effusion; tyrosine kinase inhibitor

Artikel in diesem Heft

  1. Frontmatter
  2. Editorial
  3. Tumor microenvironment and systemic disease: a dual target in medical oncology (also in the case of biomarkers)
  4. Reviews
  5. Sample types applied for molecular diagnosis of therapeutic management of advanced non-small cell lung cancer in the precision medicine
  6. The impact of pneumatic tube system on routine laboratory parameters: a systematic review and meta-analysis
  7. Opinion Paper
  8. How to reduce scientific irreproducibility: the 5-year reflection
  9. EFLM Paper
  10. Strategies to define performance specifications in laboratory medicine: 3 years on from the Milan Strategic Conference
  11. General Clinical Chemistry and Laboratory Medicine
  12. Intensive educational efforts combined with external quality assessment improve the preanalytical phase in general practitioner offices and nursing homes
  13. Separate patient serum sodium medians from males and females provide independent information on analytical bias
  14. Are admission procalcitonin levels universal mortality predictors across different medical emergency patient populations? Results from the multi-national, prospective, observational TRIAGE study
  15. Biochemical testing in a laboratory tent and semi-intensive care of Ebola patients on-site in a remote part of Guinea: a paradigm shift based on a bleach-sensitive point-of-care device
  16. Efficient reporting of the estimated glomerular filtration rate without height in pediatric patients with cancer
  17. Evaluation of thyroid test utilization through analysis of population-level data
  18. Relation of serum γ-glutamyl transferase activity with copper in an adult population
  19. Impact of a single oral dose of 100,000 IU vitamin D3 on profiles of serum 25(OH)D3 and its metabolites 24,25(OH)2D3, 3-epi-25(OH)D3, and 1,25(OH)2D3 in adults with vitamin D insufficiency
  20. Automated antinuclear immunofluorescence antibody analysis is a reliable approach in routine clinical laboratories
  21. Infrared analyzers for breast milk analysis: fat levels can influence the accuracy of protein measurements
  22. Hematology and Coagulation
  23. A new approach to define acceptance limits for hematology in external quality assessment schemes
  24. The effects of transport by car on coagulation tests
  25. Combined measurement of factor XIII and D-dimer is helpful for differential diagnosis in patients with suspected pulmonary embolism
  26. Reference Values and Biological Variations
  27. Influence of age, gender and body mass index on late-night salivary cortisol in healthy adults
  28. Cancer Diagnostics
  29. Assessment of real-time PCR method for detection of EGFR mutation using both supernatant and cell pellet of malignant pleural effusion samples from non-small-cell lung cancer patients
  30. Detection of EGFR mutations in patients with non-small cell lung cancer by high resolution melting. Comparison with other methods
  31. Predicting outcomes of EGFR-targeted therapy in non-small cell lung cancer patients using pleural effusions samples and peptide nucleic acid probe assay
  32. Analytical and clinical performance of thyroglobulin autoantibody assays in thyroid cancer follow-up
  33. Thyroglobulin autoantibodies before radioiodine ablation predict differentiated thyroid cancer outcome
  34. Cardiovascular Diseases
  35. Real life dabigatran and metabolite concentrations, focused on inter-patient variability and assay differences in patients with atrial fibrillation
  36. Infectious Diseases
  37. HIV avidity index performance using a modified fourth-generation immunoassay to detect recent HIV infections
  38. Letters to the Editor
  39. Effect of age on serum prostate-specific antigen in women
  40. Falsely elevated thyroid-stimulating hormone value due to anti-ruthenium antibodies in a patient with primary hypothyroidism: a case report
  41. High titers of anti-infliximab antibody do not interfere with Abbott immunoassays
  42. Extraordinarily elevated serum CA19-9 in a patient with posterior mediastinum cyst: a case report
  43. Low levels of 25-OH vitamin D in women with endometriosis and associated pelvic pain
  44. Evaluation of serum cortisol biological variation in the evening withdrawal
  45. Distinction between urine crystals by automated urine analyzer SediMAX conTRUST is specific but lacks sensitivity
  46. Impact of heat-inactivation on anti-Toxoplasma IgM antibody levels
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