Department of Diagnostic Innovation, Foundation IRCCS National Cancer Institute, Milan, Italy.
Department of Oncology and Hematoncology, University of Milan, Milan, Italy.
Cancer Biomark. 2023;38(3):301-309. doi: 10.3233/CBM-220357.
Pan-TRK inhibitors Entrectinib and Larotrectinib have been recently approved as tumor-agnostic therapies in NTRK1-2-3 rearranged patients and there is therefore an urgent need to identify reliable and accessible biomarkers for capturing NTRK fusions in the real-world practice.
We aim to assess the analytical validity of the recently released pan-TRK assay (Ventana), running a head-to-head comparison between immunohistochemistry and Archer FusionPlex Lung Panel (ArcherDX) that is designed to detect key fusions in 13 genes, also including NTRK1-3.
Pan-TRK IHC and NGS analysis were conducted on a retrospective/prospective cohort of 124 cancer patients (carcinomas, 93 cases; soft tissue sarcomas, 19; primary central nervous system tumours, 10; and neuroblastomas, 2). FISH data were available in most of the IHC/NGS discordant cases.
A comparison between IHC and NGS results was carried out in 117 cases: among 30 pan-TRK positive cases, NTRK rearrangement by NGS was found in 11 (37%), while one of the 87 (1.1%) pan-TRK negative cases (a case of NSCLC) showed a TPM3-NRTK1 rearrangement by NGS. Accordingly, sensitivity and specificity of IHC in predicting NTRK status were 91.7% and 81.9%, respectively, while negative (NPV) and positive predictive value (PPV) were 98.8% and 36.7%, respectively.
These data lead to suggest that IHC with VENTANA pan-TRK antibody can be a reliable screening tool for the identification of patients potentially bearing NTRK rearranged tumours.
恩曲替尼（Entrectinib）和拉罗替尼（Larotrectinib）作为泛 TRK 抑制剂，最近已被批准用于治疗 NTRK1-2-3 重排的肿瘤患者，因此迫切需要找到可靠且易于获取的生物标志物，以便在实际操作中检测 NTRK 融合。
我们旨在评估最近发布的泛 TRK 检测试剂盒（Ventana）的分析有效性，通过免疫组化（IHC）与 Archer FusionPlex Lung Panel（ArcherDX）进行头对头比较，后者旨在检测 13 个基因中的关键融合，其中也包括 NTRK1-3。
对 124 例癌症患者（癌 93 例，软组织肉瘤 19 例，原发性中枢神经系统肿瘤 10 例，神经母细胞瘤 2 例）的回顾性/前瞻性队列进行了 pan-TRK IHC 和 NGS 分析。大多数 IHC/NGS 不一致的病例均有 FISH 数据。
在 117 例病例中进行了 IHC 和 NGS 结果的比较：在 30 例 pan-TRK 阳性病例中，通过 NGS 发现 NTRK 重排在 11 例（37%）中，而在 87 例（1.1%）pan-TRK 阴性病例（1 例非小细胞肺癌）中，通过 NGS 发现 TPM3-NRTK1 重排。因此，IHC 预测 NTRK 状态的敏感性和特异性分别为 91.7%和 81.9%，阴性预测值（NPV）和阳性预测值（PPV）分别为 98.8%和 36.7%。
这些数据表明，VENTANA pan-TRK 抗体的 IHC 可以作为识别可能存在 NTRK 重排肿瘤的患者的可靠筛选工具。
