Choi Sangjoon, Park Sujin, Cho Yoon Ah, Park Cheol-Keun, Ha Sang Yun
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, South Korea.
Anatomic Pathology Reference Lab, Seegene Medical Foundation, Seoul, Republic of Korea.
Pathol Oncol Res. 2020 Oct;26(4):2587-2595. doi: 10.1007/s12253-020-00871-7. Epub 2020 Jul 4.
Oncogenic fusion of the tropomyosin receptor kinase (Trk) receptor family encoded by the NTRK gene has been found in several carcinomas. About ten targeted therapies have been developed and clinical trials are in progress. However, the results of studies on expression of the Trk receptor in HCC have not yet been published. Immunohistochemical staining was performed using anti-TrkA+B+C antibody (ab181560, Abcam) in 288 curatively resected primary HCC samples, and the correlation between Trk expression and NTRK copy number was assessed. Targeted next generation sequencing was performed in cases with Trk overexpression to detect NTRK fusion genes. Overexpression of Trk protein was observed in 21 (7.3%) of 288 cases. The Trk overexpression group showed a trend toward shorter recurrence-free survival (RFS) (p = 0.092) and overall survival (OS) (p = 0.079) than the low expression group, with frequent multicentric occurrence. Differences in RFS and OS were statistically significant in specific sub-populations including AJCC T1 stage HCCs, tumors less than 5 cm, patients without cirrhosis, tumors without vascular invasion, or Edmondson grades I and II. Trk expression was also an independent prognostic factor in both RFS and OS. Trk expression was not associated with copy number of each NTRK gene, and NTRK fusion was not detected in HCCs with Trk overexpression. Trk expression might play an important role in the development and progression of HCC, and emerging target therapy against the Trk protein could be applicable in patients with Trk-overexpressing HCC.
在多种癌症中发现了由NTRK基因编码的原肌球蛋白受体激酶（Trk）受体家族的致癌融合。目前已开发出约十种靶向疗法，临床试验正在进行中。然而，关于Trk受体在肝癌中表达的研究结果尚未发表。使用抗TrkA+B+C抗体（ab181560，Abcam）对288例根治性切除的原发性肝癌样本进行免疫组织化学染色，并评估Trk表达与NTRK拷贝数之间的相关性。对Trk过表达的病例进行靶向二代测序以检测NTRK融合基因。288例病例中有21例（7.3%）观察到Trk蛋白过表达。与低表达组相比，Trk过表达组的无复发生存期（RFS）（p = 0.092）和总生存期（OS）（p = 0.079）有缩短趋势，且多中心发生频繁。在特定亚组中，包括美国癌症联合委员会（AJCC）T1期肝癌、直径小于5 cm的肿瘤、无肝硬化的患者、无血管侵犯的肿瘤或Edmondson分级为I级和II级的患者，RFS和OS的差异具有统计学意义。Trk表达也是RFS和OS的独立预后因素。Trk表达与每个NTRK基因的拷贝数无关，在Trk过表达的肝癌中未检测到NTRK融合。Trk表达可能在肝癌的发生和发展中起重要作用，针对Trk蛋白的新兴靶向治疗可能适用于Trk过表达的肝癌患者。
