Jiang Y Y, Chen H, Xu B L, Wang S
Department of Pathology, School of Basic Medicine Sciences, Southern Medical University, Guangzhou 510515, China Department of Pathology, Shenzhen People's Hospital, Shenzhen 518002, China.
Department of Pathology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China.
Zhonghua Bing Li Xue Za Zhi. 2022 Aug 8;51(8):726-732. doi: 10.3760/cma.j.cn112151-20220117-00038.
To investigate the frequency of neurotrophic tyrosine receptor kinase (NTRK) gene variations in papillary thyroid carcinoma (PTC) and to analyze the feasibility of detecting tropomyosin receptor kinase (TRK) proteins using immunohistochemistry (IHC) to predict the fusion variation of NTRK. A cohort of 848 PTC cases was collected at the Department of Pathology, Shenzhen People's Hospital from June 2017 to June 2020. The expression levels of TRK proteins were detected using IHC in 848 PTC samples, and the DNA-based next generation sequencing (NGS) was performed to detect NTRK rearrangements in 150 PTCs. There were 242 males and 606 females, with an age range of 9-83 years. In 120 cases with TRK expression detected by IHC, 13 cases were confirmed to harbor a NTRK gene fusion by NGS. The frequency of NTRK fusion in PTC was 1.5% (13/848). The sensitivity and specificity of TRK-IHC positivity for screening NTRK fusion in PTC were 100% and 21.9%, respectively. The specificity of weak-, moderate- and strong-positive stains of TRK IHC were 23.8%, 76.9% and 93.8%, respectively. The specificity of NTRK gene fusion was predicted to increase with the enhanced intensity of IHC staining. In BRAF V600E negative PTC samples, the specificity of weak-and moderate-positive stains of TRK IHC increased to 62.5% and 96.8%, respectively. Seven NTRK fusion partners were found in the PTC, including EML4, ETV6, CDH1, GJD2, TPR, TFG and SQSTM1. There is a low variation frequency of NTRK gene fusion in PTC. TRK IHC can be used as a screening method for NTRK fusion variation in PTC. The specificity of TRK IHC predicting NTRK fusion can be further enhanced by increasing the cutoff value of the positive cell number and staining intensity of TRK-IHC staining, or being combined with BRAF V600E negativity.
探讨甲状腺乳头状癌（PTC）中神经营养性酪氨酸受体激酶（NTRK）基因变异的频率，并分析采用免疫组织化学（IHC）检测原肌球蛋白受体激酶（TRK）蛋白以预测NTRK融合变异的可行性。2017年6月至2020年6月期间，在深圳市人民医院病理科收集了848例PTC病例。采用IHC检测848例PTC样本中TRK蛋白的表达水平，并对150例PTC进行基于DNA的二代测序（NGS）以检测NTRK重排。其中男性242例，女性606例，年龄范围为9至83岁。在通过IHC检测到TRK表达的120例病例中，有13例经NGS证实存在NTRK基因融合。PTC中NTRK融合的频率为1.5%（13/848）。TRK-IHC阳性筛查PTC中NTRK融合的敏感性和特异性分别为100%和21.9%。TRK IHC弱阳性、中度阳性和强阳性染色的特异性分别为23.8%、76.9%和93.8%。预计NTRK基因融合的特异性会随着IHC染色强度增强而增加。在BRAF V600E阴性的PTC样本中，TRK IHC弱阳性和中度阳性染色的特异性分别增至62.5%和96.8%。在PTC中发现了7种NTRK融合伴侣，包括EML4、ETV6、CDH1GJD2、TPR、TFG和SQSTM1。PTC中NTRK基因融合的变异频率较低。TRK IHC可作为PTC中NTRK融合变异的筛查方法。通过提高TRK-IHC染色阳性细胞数和染色强度的临界值，或与BRAF V600E阴性相结合，可进一步提高TRK IHC预测NTRK融合的特异性。
