TY - JOUR
T1 - Histo-molecular characterization of pancreatic cancer with microsatellite instability
T2 - intra-tumor heterogeneity, B2M inactivation, and the importance of metastatic sites
AU - Luchini, Claudio
AU - Mafficini, Andrea
AU - Chatterjee, Deyali
AU - Piredda, Maria L.
AU - Sciammarella, Concetta
AU - Navale, Pooja
AU - Malleo, Giuseppe
AU - Mattiolo, Paola
AU - Marchegiani, Giovanni
AU - Pea, Antonio
AU - Salvia, Roberto
AU - Brosens, Lodewijk A.
AU - Paolino, Gaetano
AU - Mastrosimini, Maria G.
AU - Silvestris, Nicola
AU - Milella, Michele
AU - Cheng, Liang
AU - Adsay, Volkan N.
AU - Lawlor, Rita T.
AU - Scarpa, Aldo
N1 - Funding Information:
This study was supported by Associazione Italiana Ricerca sul Cancro (AIRC 5x1000 n. 12182); Fondazione Cariverona: Oncology Biobank Project “Antonio Schiavi” (prot. 203885/2017); Fondazione Italiana Malattie Pancreas (FIMP-Ministero Salute J38D19000690001); and Italian Ministry of Health (RF CO-2019-12369662: CUP: B39C21000370001).
Funding Information:
This study was supported by Associazione Italiana Ricerca sul Cancro (AIRC 5x1000 n. 12182); Fondazione Cariverona: Oncology Biobank Project “Antonio Schiavi” (prot. 203885/2017); Fondazione Italiana Malattie Pancreas (FIMP-Ministero Salute J38D19000690001); and Italian Ministry of Health (RF CO-2019-12369662: CUP: B39C21000370001).
Publisher Copyright:
© 2021, Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
KW - B2M
KW - Immunotherapy
KW - Microsatellite
KW - Pancreatic cancer
KW - Pancreatic ductal adenocarcinoma
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UR - http://www.scopus.com/inward/citedby.url?scp=85116433722&partnerID=8YFLogxK
U2 - 10.1007/s00428-021-03205-3
DO - 10.1007/s00428-021-03205-3
M3 - Article
C2 - 34613461
AN - SCOPUS:85116433722
SN - 0945-6317
VL - 480
SP - 1261
EP - 1268
JO - Virchows Archiv
JF - Virchows Archiv
IS - 6
ER -