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NTRK fusion protein expression is absent in a large cohort of diffuse large B-cell lymphoma
Susanne Ghandili1, Judith Dierlamm1, Carsten Bokemeyer1
1Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, University Cancer Center Hamburg, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Background:
Even though two NTRK-targeting drugs are available for the treatment of irresectable, metastatic, or progressive NTRK-positive solid tumors, less is known about the role of NTRK fusions in lymphoma. For this reason, we aimed to investigate if NTRK fusion proteins are expressed in diffuse large B-cell lymphoma (DLBCL) by systemic immunohistochemistry (IHC) screening and additional FISH analysis in a large cohort of DLBCL samples according to the ESMO Translational Research and Precision Medicine Working Group recommendations for the detection of NTRK fusions in daily practice and clinical research.
Methods:
A tissue microarray of 92 patients with the diagnosis of DLBCL at the University Hospital Hamburg between 2020 and 2022 was built. The clinical data were taken from patient records. Immunohistochemistry for Pan-NTRK fusion protein was performed and positive staining was defined as any viable staining. For FISH analysis only results with quality 2 and 3 were evaluated.
Results:
NTRK immunostaining was absent in all analyzable cases. No break apart was detectable by FISH.
Conclusion:
Our negative result is consistent with the very sparse data existing on NTRK gene fusions in hematologic neoplasms. To date, only a few cases of hematological malignancies have been described in which NTRK-targeting drugs may provide a potential therapeutic agent. Even though NTRK fusion protein expression was not detectable in our sample cohort, performing systemic screenings for NTRK fusions are necessary to define further the role of NTRK fusions not only in DLBCL but in a multitude of lymphoma entities as long as the lack of reliable data exists.
Insights
NTRK fusions were not detected in diffuse large B-cell lymphoma (DLBCL) using immunohistochemistry and FISH. Further research is needed to understand the role of NTRK fusions in various lymphoma types.
Area of Science:
- Oncology
- Hematology
- Molecular Diagnostics
Background:
- NTRK-targeting drugs are approved for solid tumors, but their role in lymphoma is unclear.
- NTRK fusions are rare in hematologic malignancies, with limited data available.
- Diffuse large B-cell lymphoma (DLBCL) is a common type of non-Hodgkin lymphoma.
Purpose of the Study:
- To investigate the expression of NTRK fusion proteins in a large cohort of DLBCL samples.
- To determine the prevalence of NTRK gene fusions in DLBCL using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH).
Main Methods:
- A tissue microarray of 92 DLBCL patients was analyzed.
- Systemic IHC screening for Pan-NTRK fusion protein was performed.
- FISH analysis was conducted to detect NTRK gene rearrangements.
Main Results:
- NTRK immunostaining was negative in all analyzable DLBCL cases.
- No NTRK gene break-apart rearrangements were detected by FISH.
- The study found no evidence of NTRK fusions in the studied DLBCL cohort.
Conclusions:
- The absence of NTRK fusions in this DLBCL cohort aligns with sparse existing data.
- Systemic screening for NTRK fusions is crucial for understanding their role in DLBCL and other lymphomas.
- Further research is warranted to fully elucidate the significance of NTRK fusions in hematologic neoplasms.
