title: Effect of Twist and Bmi1 on intraductal papillary mucinous neoplasm of the pancreas.
abstract: BACKGROUND
  Intraductal papillary mucinous neoplasm (IPMN) is a well-established entity among pancreatic neoplasms that ranges from low-grade dysplasia to invasive carcinoma. Epithelial-mesenchymal transition (EMT) contributes to tumor progression in various cancers. Moreover, Notch signaling is one of the important upstream effectors of EMT promotion. Currently, it is unclear whether EMT causes pathological progression of IPMN.
  
  
  OBJECTIVE
  We evaluated the expression of EMT-promoting transcription factors Twist and B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi1) in IPMN.
  
  
  METHODS
  Patients who underwent resections at our institute and its affiliated hospital were enrolled in this study (n = 35). Protein expression of EMT markers Twist, Bmi1, Jagged1, and E-cadherin in resected specimens was investigated by immunohistochemistry. Expression of these proteins was compared with the clinicopathological factors and patient survival.
  
  
  RESULTS
  Positive expression of Twist and Bmi1 was observed in 40.0% and 42.9% of IPMNs, respectively. Twist and Bmi1 expression was significantly higher in IPMNs with high-grade dysplasia (P < 0.05) and invasive carcinoma (P < 0.05) than that in IPMNs with low-grade dysplasia. High expression of Twist was correlated with Jagged1 expression and inversely correlated with expression of E-cadherin (P = 0.06 and P < 0.05, respectively). In survival analyses, the recurrence rate was significantly higher in the group that showed simultaneous high expression of Twist and Bmi1 (P < 0.05).
  
  
  CONCLUSIONS
  Expression of Twist and Bmi1 is associated with aggressiveness and poor prognoses of IPMN through EMT promotion that might be induced by Notch signaling.
authors.affiliation: Department of Surgery, The University of Tokushima, Tokushima, Japan.
authors.forename: Daichi
authors.initials: D
authors.lastname: Ishikawa
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: Tetsuya
authors.initials: T
authors.lastname: Ikemoto
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Arakawa
authors.forename: Mami
authors.initials: M
authors.lastname: Kanamoto
authors.forename: Shuichi
authors.initials: S
authors.lastname: Iwahashi
authors.forename: Yu
authors.initials: Y
authors.lastname: Saito
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Yamada
authors.forename: Hidenori
authors.initials: H
authors.lastname: Miyake
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology*; D000368:Aged; D002291:Carcinoma, Papillary / Q000235:genetics* / Q000473:pathology*; D018450:Disease Progression; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015870:Gene Expression / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics* / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D063150:Polycomb Repressive Complex 1 / Q000235:genetics* / Q000502:physiology*; D011379:Prognosis; D051880:Receptors, Notch / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051879:Twist-Related Protein 1 / Q000235:genetics* / Q000502:physiology*
chemical_list: C069077:BMI1 protein, human; D009687:Nuclear Proteins; D051880:Receptors, Notch; C103173:TWIST1 protein, human; D051879:Twist-Related Protein 1; D063150:Polycomb Repressive Complex 1
keywords: Bmi1; Twist; cancers: biology; diagnosis and therapy; epithelial-mesenchymal transition; pancreatic neoplasms: biology and therapy