Testing for ROS1 , ALK , MET , and HER2 rearrangements and amplifications in a large series of biliary tract adenocarcin
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ORIGINAL ARTICLE
Testing for ROS1, ALK, MET, and HER2 rearrangements and amplifications in a large series of biliary tract adenocarcinomas Jeremy Augustin 1,2 & Caroline Gabignon 1 & Aurélie Scriva 1 & Laëtitia Menu 2 & Claire Calmel 2 & Olivier Scatton 2,3 & François Paye 2,4 & Jean-François Fléjou 1,2 & Françoise Praz 2,5 & Pascale Cervera 1,2 & Dominique Wendum 1,2 Received: 9 May 2019 / Revised: 8 April 2020 / Accepted: 21 April 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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 HER2amplified 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 overrepresentation 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 overrepresentation of centromeric alpha-satellite sequences in intrahepatic cholangiocarcinomas. Keywords Biliary tract adenocarcinoma . HER2 . MET . ROS1 . Fluorescent in situ hybridization . Immunohistochemistry
Pascale Cervera and Dominique Wendum contributed equally to this work. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00428-020-02822-8) contains supplementary material, which is available to authorized users. * Pascale Cervera [email protected] 1
Service d’Anatomie et Cytologie Pathologiques, AP-HP, Hôpital Saint Antoine, 75012 Paris, France
2
INSERM UMR_S 938, Centre de Recherche Saint-Antoine (CRSA), Faculté de Médecine Sorbonne Université, 75012 Paris, France
3
Service de Chirurgie Hépato-Biliaire et Transplantation Hépatique, AP-HP, Hôpital Saint Antoine,
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