Department of Surgical, Medical, Molecular Pathology and Critical Area, University of Pisa, 56126 Pisa, Italy.
Pathology Unit, USL Toscana Nord-Ovest, 54033 Carrara, Italy.
Int J Mol Sci. 2022 Jul 5;23(13):7470. doi: 10.3390/ijms23137470.
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.
患有携带重排的晚期甲状腺癌的患者可以用高效的选择性抑制剂进行治疗。免疫组织化学（IHC）分析，用于检测 Trk 蛋白表达，代表了一种有吸引力的筛选策略，用于检测重排，但在甲状腺癌中其效果尚未得到充分探索。本研究旨在探讨 Trk IHC 在鉴定重排中的诊断效用。使用Ventana 系统上的泛 Trk 单克隆抗体（克隆 EPR17341），对 26 例滤泡源性甲状腺肿瘤和 28 例融合阴性对照进行了回顾性分析，这些肿瘤均为阳性 重排。通过 ROC 分析计算曲线下面积（AUC）、灵敏度和特异性。在 25 个样本中检测到 Trk 表达，包括 26 个重排中的 22 个（84.6%）和 28 个阴性样本中的 3 个（10.7%）。26 个重排甲状腺肿瘤中有 4 个（15.4%）的 Trk 表达为阴性，均携带 融合。AUC、灵敏度和特异性分别为 0.87、0.85 和 0.89。基于 IHC 分析的筛选在鉴定重排肿瘤方面显示出有限的灵敏度和特异性。由于假阴性结果可能会排除有效靶向药物的使用，因此应考虑替代检测策略用于甲状腺癌。
