Histo-molecular characterization of pancreatic cancer with microsatellite instability: intra-tumor heterogeneity, B2M inactivation, and the importance of metastatic sites.
B2M
Immunotherapy
Microsatellite
Pancreatic cancer
Pancreatic ductal adenocarcinoma
Journal
Virchows Archiv : an international journal of pathology
ISSN: 1432-2307
Titre abrégé: Virchows Arch
Pays: Germany
ID NLM: 9423843
Informations de publication
Date de publication:
Jun 2022
Jun 2022
Historique:
received:
13
07
2021
accepted:
10
09
2021
revised:
28
08
2021
pubmed:
7
10
2021
medline:
14
6
2022
entrez:
6
10
2021
Statut:
ppublish
Résumé
Pancreatic ductal adenocarcinoma (PDAC) with microsatellite instability (MSI)/defective mismatch repair (dMMR) is the only subtype of pancreatic cancer with potential response to immunotherapy. Here, we report the histo-molecular characterization of MSI/dMMR PDAC with immunohistochemistry, MSI-based PCR, and next-generation sequencing. Five paradigmatic cases have been identified. The main results include the first report in pancreatic cancer of MSI/dMMR intra-tumor heterogeneity, the presence of microsatellite-stable metastases from MSI/dMMR primary and recurrent B2M gene inactivation, which may confer resistance to immunotherapy. In addition to the classic PDAC drivers, ARID1A was the most common mutated gene in the cohort. Intra-tumor heterogeneity, B2M inactivation, and metastatic sites should be carefully considered in MSI/dMMR PDAC, which should also be investigated in routine diagnostic practice with specific molecular analysis. The chromatin remodeler ARID1A represents another potential driver gene in this context.
Identifiants
pubmed: 34613461
doi: 10.1007/s00428-021-03205-3
pii: 10.1007/s00428-021-03205-3
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1261-1268Subventions
Organisme : associazione italiana per la ricerca sul cancro
ID : 12182
Organisme : fondazione cariverona: oncology biobank project "antonio schiavi"
ID : 203885/2017
Organisme : fondazione italiana malattie pancreas
ID : J38D19000690001
Organisme : italian ministry of health
ID : RF CO-2019-12369662: CUP: B39C21000370001
Informations de copyright
© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.
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