Patterns and Relevance of Langerhans Islet Invasion in Pancreatic Cancer

dc.contributor.authorGoess, Ruediger
dc.contributor.authorMutgan, Ayse Ceren
dc.contributor.authorCalisan, Umut
dc.contributor.authorErdogan, Yusuf Ceyhun
dc.contributor.authorRen, Lei
dc.contributor.authorJager, Carsten
dc.contributor.authorSafak, Okan
dc.contributor.authorStupakov, Pavel
dc.contributor.authorIstvanffy, Rouzanna
dc.contributor.authorFriess, Helmut
dc.contributor.authorCeyhan, Guralp O.
dc.contributor.authorDemir, Ihsan Ekin
dc.date.accessioned2023-02-21T12:37:59Z
dc.date.available2023-02-21T12:37:59Z
dc.date.issued2021-01-01
dc.description.abstractSimple Summary The pathogenesis of pancreatic cancer-associated diabetes mellitus is poorly understood. We analyzed tumor infiltration into Langerhans islets and characterized it systematically for the first time, identifying four different main patterns of islet invasion. In a cohort of 68 pancreatic ductal adenocarcinoma (PDAC) patients, these islet invasion patterns were not related to occurrence of diabetes mellitus. However, severe islet invasion was associated with worsened overall survival. Background: Pancreatic cancer-associated diabetes mellitus (PC-DM) is present in most patients with pancreatic cancer, but its pathogenesis remains poorly understood. Therefore, we aimed to characterize tumor infiltration in Langerhans islets in pancreatic cancer and determine its clinical relevance. Methods: Langerhans islet invasion was systematically analyzed in 68 patients with pancreatic ductal adenocarcinoma (PDAC) using histopathological examination and 3D in vitro migration assays were performed to assess chemoattraction of pancreatic cancer cells to islet cells. Results: Langerhans islet invasion was present in all patients. We found four different patterns of islet invasion: (Type I) peri-insular invasion with tumor cells directly touching the boundary, but not penetrating the islet
dc.description.abstract(Type II) endo-insular invasion with tumor cells inside the round islet
dc.description.abstract(Type III) distorted islet structure with complete loss of the round islet morphology
dc.description.abstractand (Type IV) adjacent cancer and islet cells with solitary islet cells encountered adjacent to cancer cells. Pancreatic cancer cells did not exhibit any chemoattraction to islet cells in 3D assays in vitro. Further, there was no clinical correlation of islet invasion using the novel Islet Invasion Severity Score (IISS), which includes all invasion patterns with the occurrence of diabetes mellitus. However, Type IV islet invasion was related to worsened overall survival in our cohort. Conclusions: We systematically analyzed, for the first time, islet invasion in human pancreatic cancer. Four different main patterns of islet invasion were identified. Diabetes mellitus was not related to islet invasion. However, more research on this prevailing feature of pancreatic cancer is needed to better understand underlying principles.
dc.description.issue2
dc.description.issueJAN
dc.description.volume13
dc.identifier.doi10.3390/cancers13020249
dc.identifier.urihttps://hdl.handle.net/11443/2321
dc.identifier.urihttp://dx.doi.org/10.3390/cancers13020249
dc.identifier.wosWOS:000611157900001
dc.publisherMDPI
dc.relation.ispartofCANCERS
dc.subjectLangerhans islet
dc.subjectislet invasion
dc.subjectpancreatic tissue destruction
dc.subjectdiabetes mellitus
dc.subjectsurvival
dc.subjectpancreatic cancer
dc.titlePatterns and Relevance of Langerhans Islet Invasion in Pancreatic Cancer
dc.typeArticle

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