L4-ALK Fusion Gene Assessment Using Metastatic Lymph e Samples Obtained by Endobronchial Ultrasound-Guided R nsbronchial Needle Aspiration

pose: Anaplastic lymphoma kinase (ALK) fusion genes represent novel oncogenes for non–small ng cancers (NSCLC). Several ALK inhibitors have been developed, and are now being evaluated in ositive NSCLC. The feasibility of detecting ALK fusion genes in samples obtained by endobronchial und-guided transbronchial needle aspiration (EBUS-TBNA) was determined. The clinicopathologic teristics of ALK-positive lung cancer were also analyzed. erimental Design: From April 2008 to July 2009, NSCLC cases with hilar/mediastinal lymph node tases detected by EBUS-TBNA were enrolled. Positive expression of ALK fusion protein was ined using immunohistochemistry, and ALK gene rearrangements were further examined to verify anslocation between ALK and partner genes using fluorescent in situ hybridization and reverse ription-PCR. Direct sequencing of PCR products was performed to identify ALK fusion variants. ults:One hundred and nine cases were eligible for the analysis using re-sliced samples. Screening of specimens with immunohistochemistry revealed ALK positivity in seven cases (6.4%), all of which sed echinoderm microtubule–associated protein-like 4–ALK fusion genes as detected by fluorescent hybridization and reverse transcription-PCR. All ALK-positive cases had an adenocarcinoma histold possessed no EGFR mutations. Compared with ALK-negative cases, ALK-positive cases were more to have smaller primary tumors (P < 0.05), to occur at a younger age (<60 years; P < 0.05), and to in never/light smokers (smoking index < 400; P < 0.01). Mucin production was frequently observed -positive adenocarcinomas (29.4%; P < 0.01). clusions: EBUS-TBNA is a practical and feasible method for obtaining tissue from mediastinal Con and hilar lymph nodes that can be subjected to multimodal analysis of ALK fusion genes in NSCLC.