ArticleVirchows Archiv : an international journal of pathology2020
Testing for ROS1, ALK, MET, and HER2 rearrangements and amplifications in a large series of biliary tract adenocarcinomas.
Article in Virchows Archiv : an international journal of pathology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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6 citing papers in PubMed, 37 citations in OpenAlex.
- Immunohistochemistry in intrahepatic cholangiocarcinoma: histological subtyping and drug selection.Frontiers in oncology · 2025Review
- MST1R-targeted therapy in the battle against gallbladder cancer.Cell & bioscience · 2024Article
- Therapeutic Implications of Ceritinib in Cholangiocarcinoma beyond ALK Expression and Mutation.Pharmaceuticals (Basel, Switzerland) · 2024Article
- An unresectable and metastatic intrahepatic cholangiocarcinoma with EML4-ALK rearrangement achieving partial response after first-line treatment with ensartinib: a case report.Frontiers in oncology · 2023Article
- Dramatic response and acquired resistance to savolitinib in advanced intrahepatic cholangiocarcinoma with MET amplification: a case report and literature review.Frontiers in oncology · 2023Article
- In Reply.The oncologist · 2021Article
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11 authors at 3 institutions in 1 country.
Funding
Abstract
Biliary tract carcinomas are divided into intrahepatic, perihilar, distal extrahepatic cholangiocarcinomas, and gallbladder adenocarcinomas. Therapies targeting ROS1, ALK, MET, and HER2 alterations are currently evaluated in clinical trials. We assessed ROS1 and ALK translocations/amplifications as well as MET and HER2 amplifications for each tumor subtype by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) in 73 intrahepatic, 40 perihilar bile duct, 36 distal extrahepatic cholangiocarcinomas, and 45 gallbladder adenocarcinomas (n = 194). By FISH, we detected targetable alterations in 5.2% of cases (n = 10): HER2 and MET amplifications were found in 4.1% (n = 8) and 1.0% (n = 2), respectively. The HER2-amplified cases were mostly gallbladder adenocarcinomas (n = 5). The MET- and HER2-amplified cases were all positive by IHC. Fourteen cases without MET amplification were positive by IHC, whereas HER2 over-expression was detected by IHC only in HER2-amplified cases. We detected no ALK or ROS1 translocation or amplification. Several alterations were consistent with aneuploidy: 24 cases showed only one copy of ROS1 gene, 4 cases displayed a profile of chromosomal instability, and an over-representation of centromeric alpha-satellite sequences was found in five cases. We confirm a relatively high rate of HER2 amplifications in gallbladder adenocarcinomas and the efficacy of IHC to screen these cases. Our results also suggest the value of IHC to screen MET amplification. Contrary to initial publications, ROS1 rearrangements seem to be very rare in biliary tract adenocarcinomas. We confirm a relatively high frequency of aneuploidy and chromosomal instability and reveal the over-representation of centromeric alpha-satellite sequences in intrahepatic cholangiocarcinomas.
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