Determining factors of endobronchial ultrasound-guided transbronchial needle aspiration specimens for lung cancer subtyping and molecular testing

OBJECTIVE: This study is to explore the determining factors for testing epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) fusion after subtyping by immunohistochemistry (IHC) using samples obtained from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). MATERIALS AND METHODS: Patients suspected with advanced lung cancer were performed EBUS-TBNA without rapid on-site evaluation(ROSE) from January 2015 to March 2016 in Shanghai Chest Hospital. All samples diagnosed as lung cancer by histopathology underwent IHC to identify subtypes. EGFR mutation and ALK fusion were tested in adenocarcinoma and non-small-cell lung cancer-not otherwise specified (NSCLC-NOS) using remnant tissue samples. RESULTS: A total of 453 patients were diagnosed with lung cancer, including 44.15% (200/453) with adenocarcinoma and 11.04% (50/453) with NSCLC-NOS. With the average passes of 3.41 ± 0.68, samples obtained from EBUS-TBNA were adequate for performing EGFR mutation and ALK fusion gene analysis in 80.4% (201/250) of specimens after routine IHC. On univariate analysis, successful molecular testing was associated with passes per lesion (P = 3.80E-05), long-axis diameters (P = 6.00E-06) and short-axis diameters (P = 4.77E-04), and pathology subtypes of lesions (P = 3.00E-03). Multivariate logistic regression revealed that passes per lesion (P = 1.00E-03), long-axis diameters (P = 3.50E-02), and pathology subtypes (P = 8.00E-03) were independent risk factors associated with successful molecular testing. CONCLUSIONS: With at least three passes of per lesion, EBUS-TBNA is an efficient method to provide adequate samples for testing of EGFR mutation and ALK gene arrangement following routine histopathology and IHC subtyping. Determining factors associated with successful pathology subtyping and molecular testing using samples obtained by EBUS-TBNA are passes of per lesion, long-axis diameter, and pathology subtypes. During the process of EBUS-TBNA, selecting larger lymph nodes and the puncturing at least 3 passes per lesion may result in higher success rate in lung cancer subtyping and molecular testing.