title: Clinical role of Notch signaling pathway in intraductal papillary mucinous neoplasm of the pancreas.
abstract: OBJECTIVE
  This study was performed to elucidate the expression of the Notch signaling pathway and its correlations to clinicopathological factors of intraductal papillary mucinous neoplasms (IPMNs). It is incontrovertible that regulatory T cells (Tregs) play an important role in tumor immunity. However, the whole mechanism of control of peripheral Tregs remains unclear. It is also known that the Notch signaling pathway is involved in Treg suppressor function. Moreover, IPMNs have a high malignant potential.
  
  
  METHODS
  Peripheral blood samples and resected specimens from 18 patients with IPMN were evaluated. All patients were pathologically diagnosed with IPMN. Resected specimens were immunohistochemically evaluated (anti-Notch1, anti-Notch2, and anti-Notch2-intracellular domain antibody staining) and compared in terms of clinicopathological factors. Peripheral Treg populations were analyzed with an automated flow cytometer.
  
  
  RESULTS
  Disease-free survival was significantly worse in the Notch1 high-expression group (P = 0.023). Notch2 family expressions were higher in intraductal papillary mucinous carcinoma (IPMC) than in intraductal papillary mucinous adenoma (IPMA) (Notch2, P = 0.012; Notch2-intracellular domain, P = 0.036). Jagged1 expression was significantly higher in IPMC than in IPMA (P < 0.05) and was significantly related to recurrence. The Treg population in peripheral blood was higher in patients with IPMC than in those with IPMA (P < 0.01).
  
  
  CONCLUSIONS
  Notch signaling, especially Jagged1 expression, reflects IPMN aggressiveness. Our data may suggest that the Notch signaling pathway is a key pathway that determines IPMN pathological aggressiveness and reflects the peripheral Treg population.
authors.affiliation: Department of Surgery, Institute of Health Biosciences, The University of Tokushima, Tokushima, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ikemoto
authors.forename: Koji
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Shimada
authors.forename: Tohru
authors.initials: T
authors.lastname: Utsunomiya
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morine
authors.forename: Satoru
authors.initials: S
authors.lastname: Imura
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Arakawa
authors.forename: Mami
authors.initials: M
authors.lastname: Kanamoto
authors.forename: Shu-ichi
authors.initials: S
authors.lastname: Iwahashi
authors.forename: Yu
authors.initials: Y
authors.lastname: Saito
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yamada
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D002135:Calcium-Binding Proteins / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology*; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D000072100:Jagged-1 Protein; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D051881:Receptor, Notch1 / Q000235:genetics / Q000502:physiology*; D051883:Receptor, Notch2 / Q000235:genetics / Q000502:physiology*; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction / Q000502:physiology*; D050378:T-Lymphocytes, Regulatory
chemical_list: D002135:Calcium-Binding Proteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; C497761:NOTCH1 protein, human; C497764:NOTCH2 protein, human; D051881:Receptor, Notch1; D051883:Receptor, Notch2; D000072099:Serrate-Jagged Proteins
keywords: Jagged1; Notch signaling; intraductal papillary mucinous neoplasms; regulatory T cell