<i><scp>ALK</scp></i>,<i><scp>ROS</scp>1</i> and <i><scp>NTRK</scp>3</i> gene rearrangements in inflammatory myofibroblastic tumours

Abstract

AIMS: The aim of this study was to elucidate the pathological features of inflammatory myofibroblastic tumour (IMT) with gene rearrangement other than ALK. METHODS AND RESULTS: We investigated anaplastic lymphoma kinase (ALK), ROS1, ETV6, NTRK3 and RET in 36 cases of IMT by using immunohistochemical (IHC) staining, fluorescence in-situ hybridization, and reverse transcription polymerase chain reaction (RT-PCR). IHC staining showed ALK and ROS1 to be positive in 22 of 36 (61.1%) and two of 36 (5.6%) cases, respectively. In one case with ROS1 positivity, IHC staining showed cytoplasmic and dot-like ROS1 expression, and RT-PCR showed the presence of the TFG-ROS1 fusion transcript. Two cases of pulmonary IMT, in a 7-year-old patient and a 23-year-old patient, had ETV6 rearrangement, and the presence of the ETV6-NTRK3 fusion transcript was confirmed in one case. These tumours were composed of hypocellular myxoid areas and highly cellular areas with rich plasmacytic infiltration; the histological features were different from those of infantile fibrosarcoma. RET rearrangement was not detected. CONCLUSIONS: These results suggest that a subset of ALK-negative IMTs have rearrangement of ROS1, ETV6 or NTRK3 as a possible oncogenic mechanism, and that the detection of these alterations may be of diagnostic value and helpful for determining promising therapeutic strategies.