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Article

Limited Accuracy of Pan-Trk Immunohistochemistry Screening for NTRK Rearrangements in Follicular-Derived Thyroid Carcinoma

by
Elisabetta Macerola
1,
Agnese Proietti
1,
Anello Marcello Poma
1,
Paola Vignali
1,
Rebecca Sparavelli
1,
Alessandro Ginori
2,
Alessio Basolo
3,
Rossella Elisei
3,
Ferruccio Santini
3 and
Fulvio Basolo
1,*
1
Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy
2
Pathology Unit, USL Toscana Nord-Ovest, 54033 Carrara, Italy
3
Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2022, 23(13), 7470; https://doi.org/10.3390/ijms23137470
Submission received: 7 June 2022 / Revised: 1 July 2022 / Accepted: 3 July 2022 / Published: 5 July 2022
(This article belongs to the Special Issue Advances in Metabolism, Immunology, Genetics in Thyroid Cancer and Thyroid Disease: From Bench to Therapy)
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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.
Keywords: thyroid cancer; NTRK; pan-Trk; immunohistochemistry thyroid cancer; NTRK; pan-Trk; immunohistochemistry

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MDPI and ACS Style

Macerola, E.; Proietti, A.; Poma, A.M.; Vignali, P.; Sparavelli, R.; Ginori, A.; Basolo, A.; Elisei, R.; Santini, F.; Basolo, F. Limited Accuracy of Pan-Trk Immunohistochemistry Screening for NTRK Rearrangements in Follicular-Derived Thyroid Carcinoma. Int. J. Mol. Sci. 2022, 23, 7470. https://doi.org/10.3390/ijms23137470

AMA Style

Macerola E, Proietti A, Poma AM, Vignali P, Sparavelli R, Ginori A, Basolo A, Elisei R, Santini F, Basolo F. Limited Accuracy of Pan-Trk Immunohistochemistry Screening for NTRK Rearrangements in Follicular-Derived Thyroid Carcinoma. International Journal of Molecular Sciences. 2022; 23(13):7470. https://doi.org/10.3390/ijms23137470

Chicago/Turabian Style

Macerola, Elisabetta, Agnese Proietti, Anello Marcello Poma, Paola Vignali, Rebecca Sparavelli, Alessandro Ginori, Alessio Basolo, Rossella Elisei, Ferruccio Santini, and Fulvio Basolo. 2022. "Limited Accuracy of Pan-Trk Immunohistochemistry Screening for NTRK Rearrangements in Follicular-Derived Thyroid Carcinoma" International Journal of Molecular Sciences 23, no. 13: 7470. https://doi.org/10.3390/ijms23137470

APA Style

Macerola, E., Proietti, A., Poma, A. M., Vignali, P., Sparavelli, R., Ginori, A., Basolo, A., Elisei, R., Santini, F., & Basolo, F. (2022). Limited Accuracy of Pan-Trk Immunohistochemistry Screening for NTRK Rearrangements in Follicular-Derived Thyroid Carcinoma. International Journal of Molecular Sciences, 23(13), 7470. https://doi.org/10.3390/ijms23137470

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