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Congenital-Infantile Fibrosarcoma
A Clinicopathologic Study of 10 Cases and Molecular Detection of the ETV6-NTRK3 Fusion Transcripts Using Paraffin-Embedded Tissues

Wei-Qi Sheng MD, Masanori Hisaoka MD, Sumika Okamoto MD, Atsuko Tanaka, Jeanne M. Meis-Kindblom MD, Lars-Gunnar Kindblom MD, Tsuyoshi Ishida MD, Takayuki Nojima MD, Hiroshi Hashimoto MD
DOI: http://dx.doi.org/10.1309/3H24-E7T7-V37G-AKKQ 348-355 First published online: 1 March 2001


Congenital-infantile fibrosarcoma (CIFS) is a relatively indolent sarcoma that should be distinguished from more aggressive spindle cell sarcomas of childhood. CIFSs have been found to have a novel recurrent reciprocal translocation t(12;15)(p13;q25) resulting in the gene fusion ETV6-NTRK3 (ETS variant gene 6; neurotrophic tyrosine kinase receptor type 3). We studied immunohistochemical expression of NTRK3, and conducted a reverse transcription–polymerase chain reaction (RT-PCR) assay to detect the ETV6-NTRK3 fusion transcripts using archival formalin-fixed paraffin-embedded tissues from 10 CIFSs. Thirty-eight other spindle cell tumors were included as controls.

The ETV6-NTRK3 fusion transcripts were identified in 7 (70%) of 10 CIFSs. Nucleotide sequence analysis showed that the fusion occurred between ETV6 exon 5 and NTRK3 exon 13. The 38 control tumors were negative for the fusion transcript. Immunohisto-chemically, CIFSs consistently expressed NTRK3. But the expression of NTRK3 also was observed in 22 of 38 control tumors. These results show the diagnostic usefulness of RT-PCR methods to detect ETV6-NTRK3 fusion transcripts in archival formalin-fixed paraffin-embedded tissue and the important role of NTRK3 in the development of CIFS, despite its being a protein of little importance in differential diagnosis.

Key Words:
  • Congenital-infantile fibrosarcoma
  • ETV6-NTRK3 fusion transcripts
  • NTRK3
  • Reverse transcription-polymerase chain reaction
  • RT-PCR
  • Immunohistochemistry