title: ALK, ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumours.
abstract: OBJECTIVE
  The aim of this study was to elucidate the pathological features of inflammatory myofibroblastic tumour (IMT) with gene rearrangement other than ALK.
  
  
  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.
authors.affiliation: Department of Anatomical Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Hidetaka
authors.initials: H
authors.lastname: Yamamoto
authors.affiliation: Department of Pathology and Clinical Laboratories, National Cancer Centre Hospital, Tokyo, Japan.
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshida
authors.affiliation: Department of Pathology, National Kyushu Cancer Center, Fukuoka, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Taguchi
authors.affiliation: Department of Anatomical Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Kohashi
authors.affiliation: Department of Anatomical Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yui
authors.initials: Y
authors.lastname: Hatanaka
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Miyazaki, Kiyotake, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamashita
authors.affiliation: Department of Pathology, Saga Medical Centre Koseikan, Saga, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Mori
authors.affiliation: Department of Anatomical Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
mesh_terms: D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005354:Fibrosarcoma / Q000175:diagnosis / Q000235:genetics*; D015321:Gene Rearrangement; D006801:Humans; D007223:Infant; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D058628:Myofibroblasts / Q000473:pathology; D009379:Neoplasms, Muscle Tissue / Q000175:diagnosis / Q000235:genetics*; D050596:Oncogene Fusion; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D020812:Receptor, trkC / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D055815:Young Adult; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D000077548:Anaplastic Lymphoma Kinase; D014408:Biomarkers, Tumor; D011505:Protein-Tyrosine Kinases; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D020794:Receptor Protein-Tyrosine Kinases; D020812:Receptor, trkC; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein; C000626173:ALK protein, human; C062333:ROS1 protein, human
keywords: ALK; ETV6; NTRK3; ROS1; inflammatory myofibroblastic tumour