Multigene mutation analysis of metastatic lymph nodes in non-small cell lung cancer diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration

Chest. 2011 Nov;140(5):1319-1324. doi: 10.1378/chest.10-3186. Epub 2011 Apr 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Antineoplastic Agents / therapeutic use
  • Biopsy, Fine-Needle
  • Carboplatin / therapeutic use
  • Carcinoma, Non-Small-Cell Lung / drug therapy
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Chi-Square Distribution
  • Cisplatin / therapeutic use
  • DNA Mutational Analysis
  • Drug Resistance, Neoplasm
  • ErbB Receptors / genetics*
  • Female
  • Gefitinib
  • Genes, p53 / genetics*
  • Genes, ras / genetics*
  • Humans
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Lymphatic Metastasis / genetics*
  • Lymphatic Metastasis / pathology*
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Prognosis
  • Quinazolines / therapeutic use
  • Retrospective Studies
  • Ultrasonography, Interventional

Substances

  • Antineoplastic Agents
  • Quinazolines
  • Carboplatin
  • EGFR protein, human
  • ErbB Receptors
  • Cisplatin
  • Gefitinib