Department of Pathology, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Jiangsu Province, China.
Department of Blood Purification Center, Huan'an FirstPeople's Hospital, Nanjing Medical University, Jiangsu Province, China.
Pathol Res Pract. 2020 Sep;216(9):153116. doi: 10.1016/j.prp.2020.153116. Epub 2020 Jul 11.
As more and more molecular markers have been identified in Intrahepatic Cholangiocarcinoma (ICC), target treatments are promising all around the world. However, geographical and ethnic variations in the ICC epidemiology suggest different genetic variance prevalence in western and eastern countries.
Six genetic variations in Chinese ICC populations were analyzed by fluorescent in situ hybridization (FISH) or Sanger sequencing, listed as IDH1/2 mutation, FGFR2 translocation, NTRK1 amplification, MDM2 amplification, HER2 amplification and MET amplification, all of which have corresponding target drugs; meanwhile, they were compared with these gene prevalence in Spanish population based on the cBioPortal database.
The incidences of IDH1/2 mutation, FGFR2 translocation, NTRK1 amplification, MDM2 amplification, HER2 amplification and MET amplification were 29.5 %, 12.9 %, 1.51 %, 2.27 %, 3.03 % and 0.75 %, respectively, in the Spanish population and 7.14 %, 5.71 %, 7.86 %, 5.71 %,4.29 % and 2.14 %, respectively, in the Chinese population. For the gene NTRK1, 11 samples showed signal apart companied amplified using FISH break-apart probes but none of them demonstrated genetic fusion by next-generation sequencing. As to clinicopathological characteristics, patients carrying IDH1/2 mutation showed longer overall survival in the Chinese population, while those carrying FGFR2 translocation tended to be younger in the Spanish population. For HER2, MDM2 and MET, gene amplification predicted protein high-expression, whereas FGFR2 translocation and NTRK1 amplification did not predict protein high-expression.
Although many target drugs have been speeded up for approval such as BGJ398 for FGFR2 fusion positive ICC patients in western countries, the beneficiary populations are very small in China. The regular target drug such as trastuzumab for HER2 amplification and Crizotinib for MET amplification may be potential candidates in target treatment based on the Chinese population.
随着越来越多的分子标志物在肝内胆管癌（ICC）中被发现，靶向治疗在全球范围内具有广阔的前景。然而，ICC 流行病学的地域和种族差异表明，西方国家和东方国家的遗传变异流行率存在不同。
通过荧光原位杂交（FISH）或 Sanger 测序分析了中国 ICC 人群中的 6 种遗传变异，这些变异被列为 IDH1/2 突变、FGFR2 易位、NTRK1 扩增、MDM2 扩增、HER2 扩增和 MET 扩增，所有这些变异都有相应的靶向药物；同时，基于 cBioPortal 数据库，将这些基因在西班牙人群中的流行率与中国人群进行了比较。
西班牙人群中 IDH1/2 突变、FGFR2 易位、NTRK1 扩增、MDM2 扩增、HER2 扩增和 MET 扩增的发生率分别为 29.5%、12.9%、1.51%、2.27%、3.03%和 0.75%，而中国人群中的发生率分别为 7.14%、5.71%、7.86%、5.71%、4.29%和 2.14%。对于基因 NTRK1，11 个样本使用 FISH 断裂探针显示信号分离伴扩增，但下一代测序未显示遗传融合。就临床病理特征而言，携带 IDH1/2 突变的患者在中国人群中的总生存时间更长，而在西班牙人群中携带 FGFR2 易位的患者往往更年轻。对于 HER2、MDM2 和 MET，基因扩增预测蛋白高表达，而 FGFR2 易位和 NTRK1 扩增不预测蛋白高表达。
尽管西方国家已加快批准针对 FGFR2 融合阳性 ICC 患者的 BGJ398 等靶向药物，但在中国受益人群非常有限。基于中国人群，常规靶向药物如曲妥珠单抗针对 HER2 扩增，克唑替尼针对 MET 扩增可能是潜在的治疗选择。
