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Spontaneous Murine Model of Anaplastic Thyroid Cancer
Published on: February 3, 2023
Limited Accuracy of Pan-Trk Immunohistochemistry Screening for NTRK Rearrangements in Follicular-Derived Thyroid
Elisabetta Macerola1, Agnese Proietti1, Anello Marcello Poma1
1Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy.
Abstract:
Patients with advanced thyroid cancer harboring NTRK rearrangements can be treated with highly effective selective inhibitors. Immunohistochemistry (IHC) analysis, to detect Trk protein expression, represents an appealing screening strategy for NTRK rearrangements, but its efficacy has been poorly explored in thyroid cancer. The aim of this study is to investigate the diagnostic utility of Trk IHC in the identification of NTRK rearrangements. A series of 26 follicular-derived thyroid tumors, positive for NTRK rearrangements, and 28 NTRK fusion-negative controls were retrospectively analyzed by IHC using the pan-Trk monoclonal antibody (clone EPR17341) on the Ventana system. Area under the curve (AUC), sensitivity and specificity were calculated by ROC analysis. Trk expression was detected in 25 samples, including 22 out of the 26 NTRK-rearranged (84.6%) and three out of 28 NTRK-negative samples (10.7%). Four out of twenty-six NTRK-rearranged thyroid tumors were negative for Trk expression (15.4%), all carrying the ETV6/NTRK3 fusion. The AUC, sensitivity and specificity were 0.87, 0.85 and 0.89, respectively. A screening based on IHC analysis showed limited sensitivity and specificity in the identification of NTRK-rearranged tumors. Since falsely negative results could preclude the administration of effective targeted drugs, alternative detection strategies should be considered for thyroid cancer.
Insights
Immunohistochemistry (IHC) for Trk protein expression shows limited accuracy in screening for NTRK rearrangements in thyroid cancer. Alternative detection methods are recommended to avoid missing potential targeted therapy candidates.
Area of Science:
- Oncology
- Molecular Diagnostics
- Cancer Biomarkers
Background:
- Advanced thyroid cancer patients with NTRK rearrangements benefit from targeted inhibitors.
- Immunohistochemistry (IHC) for Trk protein is a potential screening tool for NTRK rearrangements.
- The diagnostic utility of Trk IHC in thyroid cancer requires further investigation.
Purpose of the Study:
- To evaluate the diagnostic accuracy of Trk IHC for identifying NTRK rearrangements in thyroid cancer.
- To assess the sensitivity and specificity of Trk IHC as a screening method.
Main Methods:
- Retrospective analysis of 26 NTRK-rearranged and 28 NTRK-fusion-negative thyroid tumors.
- Immunohistochemistry (IHC) using pan-Trk antibody (clone EPR17341) on Ventana system.
- Receiver Operating Characteristic (ROC) analysis to calculate Area Under the Curve (AUC), sensitivity, and specificity.
Main Results:
- Trk expression was detected in 84.6% of NTRK-rearranged tumors and 10.7% of NTRK-negative tumors.
- 15.4% of NTRK-rearranged tumors (all with ETV6/NTRK3 fusion) were negative for Trk expression.
- The AUC, sensitivity, and specificity of Trk IHC were 0.87, 0.85, and 0.89, respectively.
Conclusions:
- Trk IHC demonstrates limited sensitivity and specificity for screening NTRK rearrangements in thyroid cancer.
- Falsely negative IHC results could prevent access to effective targeted therapies.
- Alternative molecular detection strategies are necessary for accurate identification of NTRK rearrangements in thyroid cancer.
