Abstract
Background
Lung cancer is the major cause of cancer death worldwide. Mediastinal lymph node staging
is important for pretreatment lung cancer management. Endobronchial ultrasound-guided
transbronchial needle aspiration (EBUS-TBNA) is a well established method for mediastinal
lymph node staging. Although EBUS-TBNA samples are much smaller than surgical lymph
node biopsies, histopathological evaluation and molecular testing can successfully
be performed. One step nucleic acid amplification (OSNA), which measures cytokeratin
19 (CK19) mRNA concentration, is a target marker that is gaining importance in quick
detection of lymph node metastases in breast cancer and other cancers. Recent publications
suggest accurate and rapid detection of lung cancer metastases in surgically removed
lymph nodes. In this study we aimed to investigate if CK19 mRNA detection via OSNA
is feasible to accurately detect lymph node metastases in lung cancer patients using
EBUS-TBNA samples.
Materials and Methods
A total of 102 EBUS-TBNA samples of 55 patients were collected. EBUS-TBNA was performed
in lymph nodes exceeding 5 mm. OSNA was performed using a ready to use amplification
kit (Lynoamp; Sysmex, Kobe, Japan) in the RD-100 I, an automated real-time detection
system (Sysmex).
Results
Histopathological analysis confirmed malignancy in 90 cases and excluded malignancy
in 12 cases. Overall sensitivity, specificity, positive predictive value, negative
predictive value, and accuracy were 78.9%, 58.3%, 93.4%, 26.9%, and 76.5%, respectively.
Conclusions
One step nucleic acid amplification is feasible for EBUS-TBNA lymph node samples of
lung cancer patients, but CK19 mRNA is an inaccurate marker, which is unlikely to
be useful as an adjuvant test for EBUS-TBNA. Further studies are required to define
the optimal sample size and sampling method.
Keywords
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References
- Global cancer statistics, 2002.CA Cancer J Clin. 2005; 55: 74-108
- Real-time endobronchial ultrasound guided transbronchial needle aspiration for sampling mediastinal lymph nodes.Thorax. 2006; 61: 795-798
- A prospective controlled trial of endobronchial ultrasound-guided transbronchial needle aspiration compared with mediastinoscopy for mediastinal lymph node staging of lung cancer.J Thorac Cardiovasc Surg. 2011; 142: 1393-1400
- Endobronchial ultrasound-guided transbronchial needle aspiration for non–small-cell lung cancer staging.Am J Respir Crit Care Med. 2014; 15: 640-649
- EBUS-TBNA provides highest RNA yield for multiple biomarker testing from routinely obtained small biopsies in non–small-cell lung cancer patients - a comparative study of three different minimal invasive sampling methods.PLoS One. 2013; 8: e77948
- Suitabilitiy of endobronchial ultrasound-guided transbronchial needle aspiration specimens for subtyping and genotyping of non–small-cell lung cancer.Am J Respir Crit Care Med. 2012; 185: 1316-1322
- Endobronchial ultrasound-guided transbronchial needle aspiration for indentifying EGFR mutations.Eur Respir J. 2010; 35: 391-395
- Multigene mutation analysis of metastatic lymph nodes in non–small-cell lung cancer diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration.Chest. 2011; 140: 1319-1324
- Accurate molecular detection of non–small-cell lung cancer metastases in mediastinal lymph nodes sampled by endoscopic ultrasound-guided needle aspiration.Chest. 2005; 127: 430-437
- Cytokeratin 19, carcinoembryonic antigen, and epithelial cell adhesion molecule detect lung cancer lymph node metastasis in endobronchial ultrasound-guided transbronchial aspiration samples.Clin Lung Cancer. 2013; 14: 704-712
- Assessment of SHOX2 methylation in EBUS-TBNA specimen improves accuracy in lung cancer staging.Ann Oncol. 2013; 24: 2866-2870
- The real-time intra-operative evaluation of sentinel lymph nodes in breast cancer patients using one step nucleic acid amplification (OSNA) and implications for clinical decision-making.Eur J Surg Oncol. 2014; 40: 150-157
- Molecular investigation of lymph nodes in colon cancer patients using one-step nucleic acid amplification (OSNA): a new road to better staging?.Cancer. 2012; 118: 6039-6045
- Multicenter study evaluating the clinical performance of the OSNA assay for the molecular detection of lymph node metastases in gastric cancer patients.Gastric Cancer. 2014; 17: 273-280
- One-step nucleic acid amplification for detecting lymph node metastasis of head and neck squamous cell carcinoma.Oral Oncol. 2012; 48: 958-963
- One-step nucleic acid amplification for detection of lymph node metastasis in lung cancer.Ann Thorac Cardiovasc Surg. 2013; 20: 181-184
- An accurate and rapid detection of lymph node metastasis in non–small-cell lung cancer patients based on one-step nucleic acid amplification assay.Lung Cancer. 2012; 78: 212-218
- A novel diagnostic method for detection of lymph node metastases.Nihon Geka Gakkai Zasshi. 2013; 114: 4-8
- Cytokeratin 19 expression in primary thoracic tumors and lymph node metastases.Lung Cancer. 2014; 86: 318-323
- The evaluation of lymph node metastasis by endobronchial ultrasound-guided transbronchial needle aspiration: crucial for selection of surgical candidates with metastatic lung tumors.J Thorac Cardiovasc Surg. 2007; 134: 1485-1490
- Efficient utilization of EBUS-TBNA samples for both diagnosis and molecular analyses.Onco Targets Ther. 2014; 7: 2061-2065
- Keratin expression in endocrine organs and their neoplasms.Endocr Pathol. 2009; 20: 1-10
- Keratin expression in human tissues and neoplasms.Histopathology. 2002; 40: 403-439
- Expression of TTF-1 and cytokeratins in primary and secondary epithelial lung tumours: correlation with histological type and grade.Histopathology. 2004; 45: 125-134
- Cytokeratins negatively regulate the invasive potential of lung cancer cell lines.Oncol Rep. 2011; 26: 763-768
- Utility of quantitative Ki-67 proliferation index and CD56 together in the cytologic diagnosis of small cell lung carcinoma and other neuroendocrine tumors.Acta Cytol. 2013; 57: 281-290
- Bronchioloalveolar carcinoma and lung adenocarcinoma: the clinical importance and research relevance of the 2004 World Health Organization pathologic criteria.J Thorac Oncol. 2006; 1: 13-19
- Typical and atypical pulmonary carcinoid tumor overdiagnosed as small-cell carcinoma on biopsy specimens: a major pitfall in the management of lung cancer patients.Am J Surg Pathol. 2005; 29: 179-187
- Anxiety and depression after cancer diagnosis: prevalence rates by cancer type, gender and age.J Affect Disord. 2012; 141: 343-351
- Depression as a predictor of disease progression and mortality in cancer patients: a meta-analysis.Cancer. 2009; 115: 5349-5361
- Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence.Arch Intern Med. 2000; 160: 2101-2107
- Depression and cancer mortality: a meta-analysis.Psychol Med. 2010; 20: 1-14
- Distress in suspected lung cancer patients following rapid and standard diagnostic programs: a prospective observational study.Psychooncology. 2015; 24: 433-441
- Time to treat: a system redesign focusing on decreasing the time from suspicion of lung cancer to diagnosis.J Thorac Oncol. 2007; 2: 1001-1006
- Epidermal growth factor receptor mutation testing in lung cancer: searching for the ideal method.Clin Cancer Res. 2007; 13: 4954-4955
- The challenge of NSCLC diagnosis and predictive analysis on small samples. Practical approach of a working group.Lung Cancer. 2012; 76: 1-18
- Evaluation of a novel endobronchial ultrasound-guided lymph node forceps in enlarged mediastinal lymph nodes.Respiration. 2013; 86: 229-236
Article info
Publication history
Published online: September 18, 2015
Accepted:
September 11,
2015
Received in revised form:
September 3,
2015
Received:
June 22,
2015
Footnotes
Clinical Trials.gov NCT02157857.
Identification
Copyright
© 2015 Elsevier Inc. All rights reserved.