Continued">Continued">Continued">ETV6-NTRK3 Rearrangement – Children Cancer Hospital Egypt 57357

ETV6-NTRK3 Rearrangement

  • Clinical Implications
    • Diagnosis of Infantile fibrosarcoma
    • Infantile fibrosarcoma: Infiltrative, rarely metastasizing fibroblastic sarcoma of infancy associated with ETV6-NTRK3 gene fusion.

    • Diagnosis of Congenital mesoblastic nephroma
    • Congenital mesoblastic nephroma: Spindle cell neoplasm of kidney.


      • Classic (24%): Has no genetic abnormality.
      • Cellular (66%): t(12;15)(p13;q25) translocation resulting in ETV6-NTRK3 fusion.

  • Diagnosis of Secretory carcinoma
  • Mammary analogue secretory carcinoma: Salivary gland tumor characterized by ETV6 translocations, identical to secretory carcinoma of breast.

  • Other tumors
    • ALK-negative inflammatory myofibroblastic tumor, some GISTs, and some radiation-induced papillary thyroid carcinoma and acute myeloid leukemia.
    • Characteristic t(12;15)(p13;q25) with ETV6-NTRK3 fusion

  • Test Description
  • Real-time PCR for quantitative detection of ETV6-NTRK3 gene rearrangement

  • Test approach
  • RNA was isolated and converted into cDNA. TaqMan Gene Expression Assay was used for quantitative polymerase chain reaction (qPCR) analysis of ETV6-NTRK3 fusion transcript. Results interpreted according to the manufacture user guide.

  • Reporting name
  • ETV6-NTRK3 Gene fusion PCR

  • Test prerequisites (To ensure timely results)
    • Patient’s demographic data.
    • Clinicopathologic information:
      • Pathology report (final or preliminary) including anatomic location.
      • History of any given therapy for cancer and its date and relation to sample sent for molecular study (i.e. pre & post therapy). Therapy includes chemo and radiotherapy, hormonal or targeted therapy.
      • Any other relevant clinical data or history.
    • Type of sample:
      • Preferred: Formalin-fixed, paraffin-embedded (FFPE) tumor tissue block.
      • Acceptable:
        • Section in Eppendorf: Up to 4 sections, each with a thickness of up to 10 μm and a surface area of up to 250 mm2 + good H&E slide for assessment.
        • Five unstained slides + one good H&E slide.
      • Specimen Minimum Volume: Two 10-micron sections of FFPE.

  • Quality Control measures
  • All samples are subject to stringent quality control measures that include:

    • From your side:
      • Double check you are fulfilling all required data before sending your sample.
      • Check that your pathologist has selected the best block in terms of tumor cellularity, with least presence of necrosis and inflammation.
      • Pretherapy sample is preferred (if underwent any cancer therapy).
    • In our lab:
      • Assessment of tissue for adequacy & tumor cellularity before any molecular analysis.
      • Matching block ID with the report ID and demographic data.
      • Matching the submitted block with the data reported in the pathology report.
    • N.B.
      • If the sample sent in Eppendorf, it is your pathology lab’s responsibility to ensure the sample in Eppendorf is corresponding to the submitted H&E slide (we can’t prepare slide from Eppendorf).
      • This test does not include a pathology consultation.

  • Test Time
  • From 3 days to 5 working days.

  • Retention of the sample
  • Client provided paraffin blocks & unstained slides (if provided) will be returned after testing is complete.

  • Selected References
    1. Sheng WQ et al: Congenital-infantile fibrosarcoma. A clinicopathologic study of 10 cases and molecular detection of the ETV6-NTRK3 fusion transcripts using paraffin-embedded tissues. Am J Clin Pathol. 115(3):348-55, 2001
    2. Argani P et al: Detection of the ETV6-NTRK3 chimeric RNA of infantile fibrosarcoma/cellular congenital mesoblastic nephroma in paraffin-embedded tissue: application to challenging pediatric renal stromal tumors. Mod Pathol. 13(1):29-36, 2000
    3. Bourgeois JM et al: Molecular detection of the ETV6-NTRK3 gene fusion differentiates congenital fibrosarcoma from other childhood spindle cell tumors. Am J Surg Pathol. 24(7):937-46, 2000
    4. Knezevich SR et al: A novel ETV6-NTRK3 gene fusion in congenital fibrosarcoma. Nat Genet. 18(2):184-7, 1998
    5. Knezevich SR et al: ETV6-NTRK3 gene fusions and trisomy 11 establish a histogenetic link between mesoblastic nephroma and congenital fibrosarcoma. Cancer Res. 58(22):5046-8, 1998
    6. Rubin BP et al: Congenital mesoblastic nephroma t(12;15) is associated with ETV6-NTRK3 gene fusion: cytogenetic and molecular relationship to congenital (infantile) fibrosarcoma. Am J Pathol. 153(5):1451-8, 1998
    7. Laé M et al: Secretory breast carcinomas with ETV6-NTRK3 fusion gene belong to the basal-like carcinoma spectrum. Mod Pathol. 22(2):291-8, 2009
    8. Arce C et al: Secretory carcinoma of the breast containing the ETV6-NTRK3 fusion gene in a male: case report and review of the literature. World J Surg Oncol. 3:35, 2005
    9. Skálová A et al: Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol. 34(5):599-608, 2010