Abstract：
:Microsatellite instability (MSI) caused by mismatch repair deficiency (dMMR) is detected in a small proportion of pancreatic ductal adenocarcinomas (PDACs). dMMR and MSI have been associated with responses of metastatic tumors, including PDACs, to immune checkpoint inhibitor therapy. We performed immunohistochemical analyses of a 445 PDAC specimens, collected from consecutive patients at multiple centers, to identify those with dMMR, based on loss of mismatch repair proteins MLH1, MSH2, MSH6, and/or PMS2. We detected dMMR in 1.6% of tumor samples; we found dMMR in a larger proportion of intraductal papillary mucinous neoplasms-related tumors (4/58, 6.9%) than non- intraductal papillary mucinous neoplasms PDAC (5/385, 1.3%) (P = .02). PDACs with dMMR contained potentially immunogenic mutations because of MSI in coding repeat sequences. PDACs with dMMR or MSI had a higher density of CD8+ T cells at the invasive front than PDACs without dMMR or MSI (P = .08; Fisher exact test). A higher proportion of PDACs with dMMR or MSI expressed the CD274 molecule (PD-L1, 8/9) than PDACs without dMMR or MSI (4/10) (P = .05). Times of disease-free survival and overall survival did not differ significantly between patients with PDACs with dMMR or MSI vs without dMMR or MSI. Studies are needed to determine whether these features of PDACs with dMMR or MSI might serve as prognostic factors.
journal_name
Gastroenterologyjournal_title
Gastroenterologyauthors
Lupinacci RM,Goloudina A,Buhard O,Bachet JB,Maréchal R,Demetter P,Cros J,Bardier-Dupas A,Collura A,Cervera P,Scriva A,Dumont S,Hammel P,Sauvanet A,Louvet C,Delpéro JR,Paye F,Vaillant JC,André T,Closset J,Emile JFdoi
10.1053/j.gastro.2017.11.009subject
Has Abstractpub_date
2018-03-01 00:00:00pages
1061-1065issue
4eissn
0016-5085issn
1528-0012pii
S0016-5085(17)36366-7journal_volume
154pub_type
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