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

Patients with advanced thyroid cancer harboring rearrangements can be treated with highly effective selective inhibitors. Immunohistochemistry (IHC) analysis, to detect Trk protein expression, represents an appealing screening strategy for 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 rearrangements. A series of 26 follicular-derived thyroid tumors, positive for rearrangements, and 28 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 -rearranged (84.6%) and three out of 28 -negative samples (10.7%). Four out of twenty-six -rearranged thyroid tumors were negative for Trk expression (15.4%), all carrying the 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 -rearranged tumors. Since falsely negative results could preclude the administration of effective targeted drugs, alternative detection strategies should be considered for thyroid cancer.