NTRK Fusions in a Sarcomas Series: Pathology, Molecular and Clinical Aspects

Area of Science:

• Oncology
• Molecular Pathology
• Genetics

Background:

• Targeting molecular alterations, particularly neurotrophic tyrosine receptor kinase (NTRK) gene fusions, has revolutionized cancer treatment, showing high response rates in various tumors.
• Metastatic sarcomas have limited therapeutic options, making the identification of targetable NTRK fusions critical for improving patient outcomes.
• Current identification relies on immunohistochemistry and molecular confirmation, but understanding the histomorphology of NTRK-fusion positive sarcomas is essential for efficient screening.

Purpose of the Study:

• To expand the histomorphological spectrum of NTRK-fused sarcomas.
• To identify NTRK fusion partners and correlate these with clinical outcomes.
• To evaluate the immunohistochemical expression pattern of pan-TRK and its correlation with the involved NTRK gene.

Main Methods:

• Investigated pan-TRK immunohistochemical expression in 70 soft tissue and bone sarcomas.
• Performed molecular techniques to confirm NTRK fusions in pan-TRK positive cases.
• Analyzed unique histological, molecular, and clinical findings in fused sarcomas.

Main Results:

• Seven out of 70 sarcomas (10%) showed pan-TRK positivity.
• Two of the seven pan-TRK positive cases harbored an NTRK3 fusion.
• Further analysis revealed unique histological, molecular, and clinical characteristics of these NTRK-fused sarcomas.

Conclusions:

• Pan-TRK immunohistochemistry is a valuable screening tool for identifying potential NTRK-fused sarcomas.
• Understanding the histomorphological features of NTRK-fused sarcomas can aid in selecting appropriate cases for molecular testing.
• This study contributes to expanding the knowledge of NTRK-fused sarcomas, potentially guiding targeted therapy selection.