title: Presence of pancreatic intraepithelial neoplasia-3 in a background of chronic pancreatitis in pancreatic cancer patients.
abstract: The clinical significance of pancreatic intraepithelial neoplasia (PanIN) lesions in non-neoplastic pancreata of pancreatic ductal adenocarcinoma (PDAC) patients remains controversial. As chronic inflammation has been recently demonstrated to promote dissemination of in situ precancerous lesions, we investigated the prognostic significance of PanINs associated with chronic pancreatitis (CP) in PDAC patients. This retrospective study analyzed 125 curatively resected PDAC specimens for the presence of PanIN and CP. Univariate and multivariate analyses were performed to identify significant predictive factors for poor disease-free survival (DFS) and overall survival (OS). Immunohistochemical staining for E-cadherin and S100A4, markers of epithelial-mesenchymal transition, was performed on resected specimens containing PanIN-3 lesions. CP was observed in 27.2% (34/125) and PanIN-3 in 25.6% (32/125) of specimens. In the presence of CP, PanIN-3 was significantly associated with decreased survival (DFS: 4.3 vs 15.5 months, P = 0.021; OS: 16.3 vs 30.9 months, P = 0.004). PanIN-3 was not a prognostic factor in the absence of CP. The presence of both PanIN-3 and CP was associated with a reduced survival compared to the other cases, in both univariate (DFS: P = 0.039; OS: P = 0.023) and multivariate (DFS: P = 0.020; OS: P = 0.076) analyses. Furthermore, E-cadherin loss and S100A4 expression were more frequently observed in PanIN-3 lesions of CP specimens than in those of non-CP specimens, although not statistically significant. PanIN-3 in association with CP is a significant prognostic factor for decreased survival in PDAC patients, suggesting that chronic inflammation may accelerate the progression of preinvasive high-grade PanIN.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: In Kyeom
authors.initials: IK
authors.lastname: Hwang
authors.affiliation: Department of Pathology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Haeryoung
authors.initials: H
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.|Department of Internal Medicine, Keimyung University School of Medicine, Dongsan Medical Center, Daegu, Korea.
authors.forename: Yoon Suk
authors.initials: YS
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Jaihwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Jai Young
authors.initials: JY
authors.lastname: Cho
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Yoo-Seok
authors.initials: YS
authors.lastname: Yoon
authors.affiliation: Department of Surgery, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Ho-Seong
authors.initials: HS
authors.lastname: Han
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
authors.forename: Jin-Hyeok
authors.initials: JH
authors.lastname: Hwang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015820:Cadherins / Q000378:metabolism; D002278:Carcinoma in Situ / Q000150:complications / Q000401:mortality* / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000150:complications / Q000401:mortality* / Q000473:pathology; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009360:Neoplastic Cells, Circulating / Q000473:pathology; D010179:Pancreas / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000150:complications / Q000401:mortality* / Q000473:pathology; D050500:Pancreatitis, Chronic / Q000150:complications*; D012189:Retrospective Studies; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000378:metabolism
chemical_list: D015820:Cadherins; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C077591:S100A4 protein, human
keywords: Chronic pancreatitis; inflammation; pancreatic cancer; pancreatic intraepithelial lesions; prognosis