ArticleApplied immunohistochemistry & molecular morphology : AIMM2017
Detecting Gene Rearrangements in Patient Populations Through a 2-Step Diagnostic Test Comprised of Rapid IHC Enrichment Followed by Sensitive Next-Generation Sequencing.
Article in Applied immunohistochemistry & molecular morphology : AIMM, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
40 citing papers in PubMed, 3 syntheses or guidelines pooled it, 80 citations in OpenAlex.
- Japanese Society of Medical Oncology/Japan Society of Clinical Oncology/Japanese Society of Pediatric Hematology/Oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors.International journal of clinical oncology · 2023Guideline
- NTRK Fusions Detection in Paediatric Sarcomas to Expand the Morphological Spectrum and Clinical Relevance of Selected Entities.Pathology oncology research : POR · 2022Pooled it
- Japan society of clinical oncology/Japanese society of medical oncology-led clinical recommendations on the diagnosis and use of tropomyosin receptor kinase inhibitors in adult and pediatric patients with neurotrophic receptor tyrosine kinase fusion-positive advanced solid tumors, cooperated by the Japanese society of pediatric hematology/oncology.International journal of clinical oncology · 2020Guideline
- Immunohistochemistry as a screening tool for NTRK gene fusions: results of a first Belgian ring trial.Virchows Archiv : an international journal of pathology · 2021Trial
- Safety and Antitumor Activity of the Multitargeted Pan-TRK, ROS1, and ALK Inhibitor Entrectinib: Combined Results from Two Phase I Trials (ALKA-372-001 and STARTRK-1).Cancer discovery · 2017Trial
- Comprehensive Immunophenotypic Profiling and Prognostic Value in Salivary Gland Mucoepidermoid Carcinoma.International dental journal · 2026Article
- Companion Diagnostics in Clinical Therapy: Current Applications and Future Directions.MedComm · 2026Review
- Fusion-Negative NTRK Overexpression Exhibit Biological Relevance in Colorectal Cancer: Implications for Prediction of Responses to Kinase Inhibitors.Pharmaceuticals (Basel, Switzerland) · 2025Article
- NTRK protein expression in NSCLC and its clinicopathological correlation.Histology and histopathology · 2025Article
- Prospective study of the real impact of fusion centered genomic assays in patient management in a national collaborative group: the GETHI-XX-16 study.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Observational
- Advances in Tissue-Agnostic Targeting in Cancer Therapeutics: Current Approvals, Challenges, and Future Directions.Oncology research · 2025Review
- Recent advances in molecular profiling of bone and soft tissue tumors.Skeletal radiology · 2024Review
- Improved guidance is needed to optimise diagnostics and treatment of patients with thyroid cancer in Europe.Endocrine · 2024Review
- Review
- NTRK gene aberrations in triple-negative breast cancer: detection challenges using IHC, FISH, RT-PCR, and NGS.The journal of pathology. Clinical research · 2023Article
- Comparison of NTRK fusion detection methods in microsatellite-instability-high metastatic colorectal cancer.Virchows Archiv : an international journal of pathology · 2023Article
- Recommended testing algorithms for NTRK gene fusions in pediatric and selected adult cancers: Consensus of a Singapore Task Force.Asia-Pacific journal of clinical oncology · 2022Article
- Limited Accuracy of Pan-Trk Immunohistochemistry Screening forInternational journal of molecular sciences · 2022Article
- Cancer: A pathologist's journey from morphology to molecular.Medical journal, Armed Forces India · 2022Review
- FFPE-Based NGS Approaches into Clinical Practice: The Limits of Glory from a Pathologist Viewpoint.Journal of personalized medicine · 2022Review
Corrections and comments
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Authors and funding
14 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Targeted therapy combined with companion diagnostics has led to the advancement of next-generation sequencing (NGS) for detection of molecular alterations. However, using a diagnostic test to identify patient populations with low prevalence molecular alterations, such as gene rearrangements, poses efficiency, and cost challenges. To address this, we have developed a 2-step diagnostic test to identify NTRK1, NTRK2, NTRK3, ROS1, and ALK rearrangements in formalin-fixed paraffin-embedded clinical specimens. This test is comprised of immunohistochemistry screening using a pan-receptor tyrosine kinase cocktail of antibodies to identify samples expressing TrkA (encoded by NTRK1), TrkB (encoded by NTRK2), TrkC (encoded by NTRK3), ROS1, and ALK followed by an RNA-based anchored multiplex polymerase chain reaction NGS assay. We demonstrate that the NGS assay is accurate and reproducible in identification of gene rearrangements. Furthermore, implementation of an RNA quality control metric to assess the presence of amplifiable nucleic acid input material enables a measure of confidence when an NGS result is negative for gene rearrangements. Finally, we demonstrate that performing a pan-receptor tyrosine kinase immunohistochemistry staining enriches detection of the patient population for gene rearrangements from 4% to 9% and has a 100% negative predictive value. Together, this 2-step assay is an efficient method for detection of gene rearrangements in both clinical testing and studies of archival formalin-fixed paraffin-embedded specimens.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.