CHRU Brest, Department of Pathology, Brest.
Inserm U1053 BaRITOn, Bordeaux, France.
Appl Immunohistochem Mol Morphol. 2020 Oct;28(9):719-724. doi: 10.1097/PAI.0000000000000825.
Patients with NTRK-rearranged tumors can be now treated using anti-TRK-targeted therapies making NTRK testing important for treatment choices in patients with advanced cancers. Pan-TRK immunohistochemistry (IHC) could be a valuable premolecular screening strategy in this field. The choice of 1 IHC method or another requires to investigate for intermethod comparison. A high frequency of pan-TRK positive tumors among salivary gland tumors makes these tumors particularly appropriate for such a technical study. In this work, we studied the intermethod agreement for 2 pan-TRK IHC methods (using A7H6R and EPR17341 clones) in a file of salivary gland tumors of different subtypes. Among 71 tumors, pan-TRK IHC was diagnosed as positive (ie, H score ≥5) in 23 and 18 cases using EPR17341 and A7H6R clones, respectively, with a good intermethod agreement in terms of positive/negative result (κ, 0.70) but only a moderate agreement considering the H score values themselves (intraclass correlation coefficient of 0.5399). Beyond the intensity of staining and the percentages of stained cells, major differences were also observed between the location and type of cells stained in positive cases between the 2 clones. The single NTRK-rearranged case in our series (ie, a NTRK3-rearranged salivary secretory carcinoma) was positive with the 2 pan-TRK antibodies. Future studies including molecularly proven NTRK-rearranged tumors remain required to further study and compare the performances of different pan-TRK clones in the screening of NTRK-rearranged cancers but it is now obvious that the staining patterns of A7H6R and EPR17341 clones are not strictly identical.
现在，携带 NTRK 基因重排的肿瘤患者可以使用抗 TRK 靶向治疗药物进行治疗，这使得 NTRK 检测对于晚期癌症患者的治疗选择非常重要。泛 TRK 免疫组织化学（IHC）可能是该领域有价值的分子前筛选策略。选择一种 IHC 方法还是另一种方法需要进行方法间比较。唾液腺癌中存在高频率的泛 TRK 阳性肿瘤，这使得这些肿瘤特别适合进行这种技术研究。在这项工作中，我们研究了两种泛 TRK IHC 方法（使用 A7H6R 和 EPR17341 克隆）在不同亚型唾液腺癌文件中的方法间一致性。在 71 个肿瘤中，使用 EPR17341 和 A7H6R 克隆，分别有 23 例和 18 例诊断为泛 TRK IHC 阳性（即 H 评分≥5），阳性/阴性结果的方法间一致性较好（κ，0.70），但仅考虑 H 评分值本身，一致性适中（组内相关系数为 0.5399）。除了染色强度和染色细胞百分比外，在阳性病例中，两种克隆之间还观察到染色细胞的位置和类型存在明显差异。我们系列中的单个 NTRK 基因重排病例（即 NTRK3 基因重排的唾液分泌癌）与两种泛 TRK 抗体均呈阳性。需要进一步研究和比较不同泛 TRK 克隆在筛查 NTRK 基因重排癌症中的性能，但目前很明显，A7H6R 和 EPR17341 克隆的染色模式并不完全相同，因此还需要包括分子证实的 NTRK 基因重排肿瘤的未来研究。
