Oncogenic Gene Transcripts Detection by FISH on Liquid-based Cytology Slides of 338 Advanced Lung Cancer Patients

Abstract Background Oncogenic gene transcripts in advanced lung cancer are a strong indication for targeted therapy. Cytology specimens are often the only materials available for oncogenic fusion analysis. This prospective study is to evaluate the feasibility of Anaplastic lymphoma kinase (ALK) gene rearrangements, ROS oncogene 1 (ROS-1), and c-mesenchymal-epidermal transformation (c-MET) detected by fluorescence in situ hybridization (FISH) using liquid-based cytology (LBC) slides. Methods Consecutive cytology specimens including fine-needle aspiration biopsy (FNAB) and serous effusions from 338 advanced lung cancer patients were collected between March 1, 2015, and July 6, 2016. The correlation between ALK, ROS-1, c-MET, and other common driver gene abnormalities and the therapeutic response to crizotinib in ALK-positive patients were also evaluated. Results ALK fusion transcripts were detected in 31 of 338 patients (9.17%). Twenty-two of the 31 ALK-positive patients were treated with crizotinib at our institution (2 were lost to follow-up), and the overall response rate was 75.0 % (15/20); disease control rate was 90.0% (18/20). FISH analyses for ROS-1 and c-MET were performed on 75 and 73 patients, respectively and showed 3 patients positive for ROS-1 and 3 positive for c-MET. These positive cases were all ALK negative. Conclusion For patients with advanced lung cancer, LBC slides are suitable for detecting oncogenic gene transcripts, and the results can provide a reliable guideline for targeted therapy.