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Screening for Melanoma Modifiers using a Zebrafish Autochthonous Tumor Model
Published on: November 13, 2012
Screening for NTRK-rearranged Tumors Using Immunohistochemistry: Comparison of 2 Different pan-TRK Clones in Melanoma
Amélie Bourhis1, Geoffroy Redoulez1, Isabelle Quintin-Roué1
1Department of Pathology, CHRU Brest, Brest.
Abstract:
NTRK-rearranged tumors could be treated using promising anti-TRK-targeted therapies in patients with advanced cancers including melanomas. Different targeted therapies are being developed together with different screening strategies including pan-TRK immunohistochemistry (IHC) as first-line screening strategies. In this technical study, we compared 2 pan-TRK IHC (using A7H6R and EPR17341 clones) in tumor samples of patients with advanced melanomas. IHC-positive cases were studied using NTRK1, NTRK2, and NTRK3 fluorescent in situ hybridization tests. Among 300 melanoma samples, 4 samples were positive using A7H6R IHC, but none using EPR17341. None of the 4 samples were NTRK-rearranged using fluorescent in situ hybridization. Different staining was also noted in nontumor kidney tissue, whereas an NTRK1-rearranged tumor used as positive control was strongly stained with both A7H6R and EPR17341 clones. Future studies including more numerous NTRK-rearranged tumors are required to further study and compare the performances of different pan-TRK clones in the screening of NTRK-rearranged cancers.
Insights
This study compared two pan-TRK immunohistochemistry (IHC) clones for screening NTRK-rearranged melanomas. Neither clone reliably identified NTRK rearrangements, highlighting the need for improved diagnostic methods for targeted cancer therapies.
Area of Science:
- Oncology
- Molecular Diagnostics
- Cancer Research
Background:
- NTRK-rearranged tumors are treatable with anti-TRK targeted therapies.
- Pan-TRK immunohistochemistry (IHC) is a primary screening method for these alterations.
- Accurate screening is crucial for effective patient treatment.
Purpose of the Study:
- To compare the diagnostic performance of two pan-TRK IHC clones (A7H6R and EPR17341).
- To evaluate their efficacy in identifying NTRK rearrangements in advanced melanoma samples.
Main Methods:
- Comparative analysis of two pan-TRK IHC clones (A7H6R, EPR17341) on 300 melanoma samples.
- Confirmation of IHC-positive cases using NTRK1, NTRK2, and NTRK3 fluorescent in situ hybridization (FISH).
- Assessment of staining in non-tumor tissues and use of a positive control.
Main Results:
- A7H6R IHC identified 4 positive samples, while EPR17341 identified none.
- None of the 4 samples positive by A7H6R IHC showed NTRK rearrangement via FISH.
- Non-specific staining was observed in kidney tissue; both clones stained the positive control.
Conclusions:
- Current pan-TRK IHC clones may have limitations in accurately screening for NTRK rearrangements in melanomas.
- Further studies with larger cohorts of confirmed NTRK-rearranged tumors are needed.
- Improved diagnostic strategies are required for selecting patients for TRK-targeted therapies.
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