title: Comparative characterization of stroma cells and ductal epithelium in chronic pancreatitis and pancreatic ductal adenocarcinoma.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extensive stroma being also present in chronic pancreatitis (CP). Using immunohistochemistry, the stroma of CP and PDAC was comprehensively analyzed and correlated with epithelial/carcinoma-related alterations and clinicopathological patient characteristics. While there were no significant differences between CP and PDAC regarding the distribution of CD3+ T cells and α-SMA+ fibroblasts, proportions of CD4+ and CD8+ T cells were significantly lower and numbers of CD25+(CD4+) and FoxP3+(CD4+) regulatory T cells were greater in PDAC compared with CP. Macrophages were more prevalent in CP, but localized more closely to carcinoma cells in PDAC, as were γδ-T cells. Duct-related FoxP3 and L1CAM expression increased from CP to PDAC, while vimentin expression was similarly abundant in both diseases. Moreover, stromal and epithelial compartments of well-differentiated tumors and CPs shared considerable similarities, while moderately and poorly differentiated tumors significantly differed from CP tissues. Analysis of 27 parameters within each pancreatic disease revealed a significant correlation of i) CD4+ and FoxP3+CD4+ T cells with FoxP3 expression in PDAC cells, ii) α-SMA+ fibroblasts with L1CAM expression and proliferation in PDAC cells, iii) CD3 and CD8 expression with γδ-TCR expression in both pancreatic diseases and iv) CD68+ and CD163+ macrophages with vimentin expression in PDAC cells. High expression of FoxP3, vimentin and L1CAM in PDAC cells as well as a tumor-related localization of macrophages each tended to correlate with higher tumor grade. Multivariate survival analysis revealed a younger age at time of surgery as a positive prognostic marker for PDAC patients with the most frequently operated disease stage T3N1M0. Overall this study identified several interrelationships between stroma and epithelial/carcinoma cells in PDACs but also in CP, which in light of previous experimental data strongly support the view that the inflammatory stroma contributes to malignancy-associated alterations already in precursor cells during CP.
authors.affiliation: Institute for Experimental Medicine, Group Inflammatory Carcinogenesis, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Ole
authors.initials: O
authors.lastname: Helm
authors.affiliation: Institute for Experimental Medicine, Group Inflammatory Carcinogenesis, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Ruben
authors.initials: R
authors.lastname: Mennrich
authors.affiliation: Institute of Immunology, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Domantas
authors.initials: D
authors.lastname: Petrick
authors.affiliation: Institute for Experimental Medicine, Group Inflammatory Carcinogenesis, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Lisa
authors.initials: L
authors.lastname: Goebel
authors.affiliation: Institute of Medical Informatics and Statistics, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Sandra
authors.initials: S
authors.lastname: Freitag-Wolf
authors.affiliation: Institute of Experimental Cancer Research, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Röder
authors.affiliation: Institute of Experimental Cancer Research, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Kalthoff
authors.affiliation: Institute of Pathology, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Röcken
authors.affiliation: Institute of Pathology; University Tübingen, Tübingen, Germany.
authors.forename: Bence
authors.initials: B
authors.lastname: Sipos
authors.affiliation: Institute of Immunology, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Kabelitz
authors.affiliation: Department of Internal Medicine I, Laboratory of Molecular Gastroenterology & Hepatology, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Heiner
authors.initials: H
authors.lastname: Schäfer
authors.affiliation: Institute of Immunology, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Hans-Heinrich
authors.initials: HH
authors.lastname: Oberg
authors.affiliation: Institute of Immunology, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Wesch
authors.affiliation: Institute for Experimental Medicine, Group Inflammatory Carcinogenesis, UKSH Campus Kiel, Kiel, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Sebens
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000943:Antigens, Differentiation / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002908:Chronic Disease; D018572:Disease-Free Survival; D004848:Epithelium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D010183:Pancreatic Ducts / Q000378:metabolism* / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D010195:Pancreatitis / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D015996:Survival Rate
chemical_list: D000943:Antigens, Differentiation; D009363:Neoplasm Proteins