ALK rearrangements in EBUS-derived transbronchial needle aspiration cytology in lung cancer.

ABSTRACT

OBJECTIVES: Patients with non-small cell lung cancer (NSCLC) positive for anaplastic lymphoma kinase (ALK) gene rearrangements may be treated successfully with the ALK inhibitor crizotinib. ALK copy-number abnormalities have also been described. In this study, we evaluated the suitability of fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) to determine ALK status in endobronchial ultrasound (EBUS)-derived cytology samples. METHODS: Samples were obtained from 55 consecutive patients with NSCLC who had undergone EBUS-transbronchial needle aspiration (TBNA) according to our standard clinical protocols. All tumours had been screened previously for epithelial growth factor receptor (EGFR) and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. FISH, using commercially available ALK rearrangement-specific probes, was employed to assess ALK status. IHC using the ALK-1 monoclonal antibody (DAKO) was also performed. RESULTS: FISH analysis was successful in 52 of 55 samples (94.5%); ALK rearrangement was demonstrated in 3 of 52 samples from patients with NSCLC (5.7%). ALK amplification was observed in 3 of 52 patient samples (5.7%) and an increase in ALK copy number was found in 28 of 52 patient samples (53.8%). IHC on cell blocks demonstrated ALK expression in one of three samples with ALK rearrangement. One patient sample had concomitant ALK rearrangement and KRAS mutation. CONCLUSIONS: We found FISH to be superior to IHC using the ALK-1 monoclonal antibody for the detection of ALK rearrangement in EBUS-TBNA cytology specimens in NSCLC, and also that ALK rearrangement can co-exist with KRAS mutation in the same tumour.