Yamashiro Yuya, Kurihara Taisei, Hayashi Takuo, Suehara Yoshiyuki, Yao Takashi, Kato Shunsuke, Saito Tsuyoshi
Department of Human Pathology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, Japan.
Department of Medicine for Orthopaedics and Motor Organ, Juntendo University Graduate School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo, Japan.
Sci Rep. 2021 Mar 11;11(1):5635. doi: 10.1038/s41598-021-85075-y.
NTRK fusion-positive tumors are known to be highly sensitive to TRK inhibitors, such as larotrectinib and entrectinib. Therefore, identification of patients who can potentially benefit from these inhibitors is important; however, the frequency of NTRK fusions in Japanese patients with colorectal cancer (CRC) is unknown. We performed pan-TRK staining using TMA-based immunohistochemistry (IHC) on samples from 971 consecutive Japanese CRC cases from a single institution. Positive cases were further analyzed using NanoString and subsequent targeted RNA sequencing. We found three positive cases using TRK-IHC. Furthermore, the Nanostring assay supported the presence of NTRK fusion in these cases. Subsequent targeted RNA-sequencing and RT-PCR revealed two cases with TPM3-NTRK1 and one with TPR-NTRK1. The TNM stages of these cases were stage I, stage IIA, and stage IIIB, and two showed microsatellite instability-high status. Next-generation sequencing analysis using Cancer hotspot panel revealed TP53 and SMAD4 mutations in separate cases. IHC of β-catenin did not show nuclear accumulation. We found three cases (0.31%) of CRC with NTRK1 fusion among 971 consecutive Japanese CRC cases. No potential driver alterations other than NTRK fusion were identified in these three patients.
已知NTRK融合阳性肿瘤对TRK抑制剂（如拉罗替尼和恩曲替尼）高度敏感。因此，识别可能从这些抑制剂中获益的患者很重要；然而，日本结直肠癌（CRC）患者中NTRK融合的频率尚不清楚。我们对来自单一机构的971例连续日本CRC病例的样本进行了基于组织微阵列（TMA）的免疫组织化学（IHC）全TRK染色。阳性病例进一步使用NanoString和随后的靶向RNA测序进行分析。我们通过TRK-IHC发现了3例阳性病例。此外，NanoString分析支持这些病例中存在NTRK融合。随后的靶向RNA测序和逆转录聚合酶链反应（RT-PCR）显示2例为TPM3-NTRK1融合，1例为TPR-NTRK1融合。这些病例的TNM分期分别为I期、IIA期和IIIB期，2例显示微卫星高度不稳定状态。使用癌症热点panel进行的二代测序分析在不同病例中发现了TP53和SMAD4突变。β-连环蛋白的免疫组化未显示核内积聚。在971例连续日本CRC病例中，我们发现3例（0.31%）CRC患者存在NTRK1融合。在这3例患者中未发现除NTRK融合以外的其他潜在驱动改变。
