Expression of CD117, CK17, CK20, MUC4, villin and mismatch repair deficiency in pancreatic intraductal papillary mucinous neoplasm

Sönke Detlefsen, Mark Jakobsen, Michael Friberg Bruun Nielsen, Günter Klöbbel, Michael Bau Mortensen

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Among pancreatic neoplasms, gastric, intestinal, and pancreatobiliary intraductal papillary mucinous neoplasm (IPMN), intraductal oncocytic papillary neoplasm (IOPN), and intraductal tubulopapillary neoplasm (ITPN) have been defined, differing regarding association with invasive carcinoma and prognosis. Immunohistochemistry (IHC) can help in the distinction of these neoplasms, but a proportion is unclassifiable using recommended markers. The frequency of the different types of IPMNs in surgical specimens from Danish patients remains to be examined. Besides, the role of mismatch repair (MMR) deficiency in these neoplasms has not been fully elucidated. We aimed to evaluate the frequency of different types of IPMN in a Danish cohort. Furthermore, we aimed to examine the utility of CD117, CK17, CK20, MUC4, and villin as markers for their distinction, in addition to the recommended markers MUC1, MUC2, MUC5AC, MUC6 and CDX2, and to evaluate the frequency of MMR deficiency. We typed 40 consecutively resected pancreatic intraductal papillary neoplasms according to the WHO criteria from 2019. IHC for CD117, CDX2, CK17, CK20, MLH1, MSH2, MSH6, MUC1 (H23), MUC1 (Ma695), MUC2, MUC4, MUC5AC, MUC6, PMS2, and villin was performed and evaluated using a five-tiered semiquantitative scale. A subset of the tumours was examined with PCR for microsatellite instability (MSI). Most tumours were intestinal (40%) and gastric (40%) IPMNs, followed by pancreatobiliary (17%) IPMNs and IOPN (3%). All cases were MMR proficient. We found a higher expression of MUC4, CK20 and villin in intestinal compared to gastric IPMNs (p < 0.01, p < 0.001 and p < 0.001). MUC4 was expressed higher in intestinal compared to pancreatobiliary IPMNs, while the opposite was found for CK17 (p < 0.05 and p < 0.05). IOPN showed strong CD117 expression (score 4), while all gastric IPMNs were negative and 50% and 29% of intestinal and pancreatobiliary IPMNs only showed weak expression (score 1). Our data suggest that CK20, MUC4 and villin may aid in the identification of intestinal IPMNs and that CK17 and CD117 may be of value for identification of pancreatobiliary IPMNs and IOPN in some cases. However, additional studies evaluating these markers in pancreatic IPMNs are needed. Abbreviations IOPNintraductal oncocytic papillary neoplasmIPMNintraductal papillary mucinous neoplasmIPNintraductal papillary neoplasmMMRmismatch repairMSImicrosatellite instableMSSmicrosatellite stable
TidsskriftPathology, Research and Practice
StatusUdgivet - dec. 2020