KIF5B/RET fusion gene analysis in a selected series of cytological specimens of EGFR, KRAS and EML4-ALK wild-type adenocarcinomas of the lung

摘要

A new RET fusion gene has been recently described in a subset of non-small cell lung cancer (NSCLC) identified by specific clinico-pathologic characteristics. This transforming gene arise from the fusion of KIF5B and the RET proto-oncogene, and it is mutually exclusive with EGFR, KRAS and EML4/ALK alterations. For this reason it could represent a putative target for specific inhibitory drugs and its evaluation could be necessary in the future daily molecular characterization of NSCLCs. One of the major challenge in diagnostic molecular pathology is to optimize genotyping tests with the minimally invasive techniques used to acquire diagnostic tumor tissue or cells. This is a significant relevant issue for approximately 60% of NSCLC patients presenting with unresectable disease, where the only pathologic materials available for diagnostic use are small biopsy or cytological specimens. Thus, the aim of this study was to verify the possibility to use RNA purified from cytological specimens to perform KIF5B/RET gene fusion expression analysis. Accordingly, we looked for the presence of the rearrangement in formalin fixed paraffin embedded tissues (FFPETs) and cytological specimens (CSs) of a selected series of "triple-marker" negative adenocarcinomas. The tests conducted revealed the presence of 1 positive patient for variant 1 of KIF5B/RET among the 49 analyzed. The presence of this fusion transcript was found in both FFPET and CS of the same patient demonstrating that the RNA obtained from minimally invasive techniques is perfectly suitable for this kind of tests. The presence of the rearrangement was also confirmed by FISH analysis.In conclusion, our findings confirm that the performance of cytology-based molecular testing for KIF5B/RET rearrangements is at least as effective as histology-based analysis, both with regard to the success rate for nucleic acid isolation and the ability to detect gene alterations.