Document Detail


Multigene mutation analysis of metastatic lymph nodes in non-small cell lung cancer diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration.
MedLine Citation:
PMID:  21527506     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
Takahiro Nakajima; Kazuhiro Yasufuku; Akira Nakagawara; Hideki Kimura; Ichiro Yoshino
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-04-28
Journal Detail:
Title:  Chest     Volume:  140     ISSN:  1931-3543     ISO Abbreviation:  Chest     Publication Date:  2011 Nov 
Date Detail:
Created Date:  2011-11-02     Completed Date:  2011-12-29     Revised Date:  2013-06-03    
Medline Journal Info:
Nlm Unique ID:  0231335     Medline TA:  Chest     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1319-24     Citation Subset:  AIM; IM    
Affiliation:
Division of Thoracic Surgery, Chiba Cancer Center, Chiba, Japan.
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MeSH Terms
Descriptor/Qualifier:
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,  genetics*,  pathology*
Chi-Square Distribution
Cisplatin / therapeutic use
DNA Mutational Analysis
Drug Resistance, Neoplasm
Female
Genes, p53 / genetics*
Genes, ras / genetics*
Humans
Lung Neoplasms / drug therapy,  genetics*,  pathology*
Lymphatic Metastasis / genetics*,  pathology*
Male
Middle Aged
Neoplasm Staging
Polymerase Chain Reaction
Prognosis
Quinazolines / therapeutic use
Receptor, Epidermal Growth Factor / genetics*
Retrospective Studies
Ultrasonography, Interventional
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Quinazolines; 15663-27-1/Cisplatin; 41575-94-4/Carboplatin; EC 2.7.10.1/EGFR protein, human; EC 2.7.10.1/Receptor, Epidermal Growth Factor; S65743JHBS/gefitinib
Comments/Corrections
Comment In:
Chest. 2011 Dec;140(6):1664; author reply 1664-5   [PMID:  22147827 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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