title: Multigene mutation analysis of metastatic lymph nodes in non-small cell lung cancer diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration.
abstract: BACKGROUND
  The importance of biomarker analysis in patients with non-small cell lung cancer (NSCLC) is well known. The purpose of this study was to analyze the mutation status of multiple genes in metastatic lymph nodes obtained by endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) and to examine the correlation between treatments and outcomes.
  
  
  METHODS
  Genetic alterations were analyzed in metastatic hilar or mediastinal lymph nodes diagnosed by EBUS-TBNA in 156 patients with NSCLC. Epidermal growth factor receptor (EGFR) was analyzed using the peptide nucleic acid-locked nucleic acid polymerase chain reaction clamp method (n = 156). V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-ras) (exons 2-3) and tumor protein 53 (p53) (exons 4-8) were analyzed by direct sequencing (n = 113). In addition, retrospective chart review was performed for clinical data analysis.
  
  
  RESULTS
  EGFR gene mutations were detected in 42 cases (26.9%). Twenty-three patients with EGFR mutations received gefitinib, with an overall response rate (partial response [PR]) of 54.5% and disease control rate (PR + stable disease) of 86.4% (Response Evaluation Criteria in Solid Tumors). K-ras gene mutations were detected in four cases (3.5%), and p53 gene mutations were detected in 47 cases (41.6%). Fifty-two patients underwent conventional chemotherapy (46 patients underwent platinum-based chemotherapy). Patients with p53 gene mutations showed chemoresistance (progressive disease of 42.9%, P = .0339) and a relatively poor prognosis after chemotherapy (P = .1391).
  
  
  CONCLUSIONS
  Multigene mutation analysis can be performed in EBUS-TBNA samples of metastatic lymph nodes from patients with NSCLC. EBUS-TBNA allows genetic evaluation of tumor cells within the metastatic node, which may allow physicians to better select treatments, particularly EGFR tyrosine kinase inhibitors.
authors.affiliation: Division of Thoracic Surgery, Chiba, Japan; Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, ON, Canada; Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Nakajima
authors.affiliation: Division of Thoracic Surgery, Toronto General Hospital, University Health Network, Toronto, ON, Canada. Electronic address: Kazuhiro.Yasufuku@uhn.on.ca.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yasufuku
authors.affiliation: Chiba Cancer Center, Chiba, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Nakagawara
authors.affiliation: Division of Thoracic Surgery, Chiba, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kimura
authors.affiliation: Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Yoshino
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use; D044963:Biopsy, Fine-Needle; D016190:Carboplatin / Q000627:therapeutic use; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D016009:Chi-Square Distribution; D002945:Cisplatin / Q000627:therapeutic use; D004252:DNA Mutational Analysis; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000235:genetics* / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011799:Quinazolines / Q000627:therapeutic use; D012189:Retrospective Studies; D018084:Ultrasonography, Interventional
chemical_list: D000970:Antineoplastic Agents; D011799:Quinazolines; D016190:Carboplatin; C512478:EGFR protein, human; D066246:ErbB Receptors; D002945:Cisplatin; D000077156:Gefitinib