The investigation of ros1 gene rearrangement in lung adenocarcinoma by fluorescent in situ hybridization (FİSH) and immunohistochemical method

Approximately 2% of the lung adenocarcinoma patients have ROS1 gene rearrangement and they are candidates of targeted therapy. Our aim is to determine the tumor subgroup having ROS1 gene rearrangement in our population and their characteristics, to investigate the correlation between immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) techniques for ROS1 gene rearrangement and to contribute to the literature by determining the algorithms that can be used for routine evaluation. The account of patients with lung adenocarcinoma included to our study was 260. Demographic findings, tumor stages at the time of diagnosis, last seen date, date of death, Epidermal growth factor receptor (EGFR) and Anaplastic lymphoma kinase (ALK) mutations were recorded from patient charts. Totally, 226 patients with adequate tumor cells were evaluated for FISH ROS1 and IHC ROS1. Before these tests, some tumor tissue samples were reprocessed by macrodissection. Male patients account for 81.5% and females were 18.5%. The age range of the patients was 29-89 and the mean age was 61.4. The most common seen subtypes were aciner pattern (39.8%) and solid pattern (34.9%). At the time of diagnosis, 57.4% of the cases were stage IV. Median survival time of the patients was 22.8 months. The EGFR mutation rate was 12.3% and the ALK mutation rate was 3.81%. ROS1 gene rearrangement was detected at a 62 year-old male patient from the metastatic lymph node biopsy. He had 40 pack-year smoking history. A solid pattern was seen. The patient's overall survival was 3.5 months. Additionally in two patients, (+1) staining was observed with ROS1 IHC. The diagnostic power of ROS1 was found weak. However, patients without ROS1 rearrangement was determined reliably in 99% by ROS1 IHC. It is important to investigate the presence of ROS1 in lung adenocarcinoma patients without EGFR and ALK mutations. It would be more economical and practical to use IHC which has been tested for reliability under laboratory-specific conditions and established as a screening test.