ALK, ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumours

Histopathology. 2016 Jul;69(1):72-83. doi: 10.1111/his.12910. Epub 2016 Jan 19.

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.

Keywords: ALK; ETV6; NTRK3; ROS1; inflammatory myofibroblastic tumour.

MeSH terms

  • Adult
  • Aged
  • Anaplastic Lymphoma Kinase
  • Biomarkers, Tumor / genetics*
  • Child
  • Child, Preschool
  • ETS Translocation Variant 6 Protein
  • Female
  • Fibrosarcoma / diagnosis
  • Fibrosarcoma / genetics*
  • Gene Rearrangement
  • Humans
  • Infant
  • Inflammation
  • Male
  • Middle Aged
  • Myofibroblasts / pathology
  • Neoplasms, Muscle Tissue / diagnosis
  • Neoplasms, Muscle Tissue / genetics*
  • Oncogene Fusion
  • Protein-Tyrosine Kinases / genetics*
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins c-ets / genetics
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Receptor, trkC / genetics*
  • Repressor Proteins / genetics
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • Repressor Proteins
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Protein-Tyrosine Kinases
  • ROS1 protein, human
  • Receptor Protein-Tyrosine Kinases
  • Receptor, trkC