Prevalence of Microsatellite Instability in Intraductal Papillary Mucinous Neoplasms of the Pancreas

Jean Bachet 1 Raphaël Maréchal Pieter Demetter 2 Jérôme Cros 3 Armelle Bardier-Dupas 4 Sylvie Dumont 5 Pascal Hammel 6 Alain Sauvanet 7 Christophe Louvet 8 Jean Delpéro Jean Vaillant 9 Jean Closset Jean-François Emile 10 Jean-Luc Van Laethem 11 Issam Abd Alsamad Martine Antoine 12 Anita Rodenas 13 Jean-François Fléjou 14 Nelson Dusetti 15 Juan Iovanna 16, 15 Alex Duval 17 Magali Svrcek 17 Renato Lupinacci Anastasia Goloudina 18 Olivier Buhard 18 Ada Collura 19 Pascal Cervera Aurélie Scriva François Paye 20 Thierry André 21 Vincent Jonchère 18
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.
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Gastroenterology, WB Saunders, 2017, 154 (4), pp.1061 - 1065. 〈10.1053/j.gastro.2017.11.009〉
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Soumis le : lundi 14 mai 2018 - 17:45:28
Dernière modification le : mercredi 18 juillet 2018 - 20:11:27

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Jean Bachet, Raphaël Maréchal, Pieter Demetter, Jérôme Cros, Armelle Bardier-Dupas, et al.. Prevalence of Microsatellite Instability in Intraductal Papillary Mucinous Neoplasms of the Pancreas. Gastroenterology, WB Saunders, 2017, 154 (4), pp.1061 - 1065. 〈10.1053/j.gastro.2017.11.009〉. 〈hal-01791680〉

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