title: CD24 and S100A4 expression in resectable pancreatic cancers with earlier disease recurrence and poor survival.
abstract: OBJECTIVE
  The objectives of this study were to study the expression status of markers associated with epithelial-to-mesenchymal transition (EMT) and metastasis in pancreatic ductal adenocarcinomas (PDACs) and to explore the prognostic value of these markers.
  
  
  METHODS
  Immunohistochemical stains for CD24, CD44, E-cadherin, N-cadherin, Snail, S100A4, Vimentin, urokinase-type plasminogen activator receptor, Ezrin, and matrix metalloproteinase 2 were performed on 67 resected PDACs.
  
  
  RESULTS
  Proteins associated with EMT and metastasis were more frequently expressed in PDACs with poor differentiation, higher tumor stage, and lymphatic and perineural invasion. CD24 expression was associated with frequent expression of EMT markers (CD44 [P = 0.004], S100A4 [P < 0.001], Vimentin [P = 0.022], urokinase-type plasminogen activator receptor [P = 0.002], and Ezrin [P = 0.010]). CD24 and S100A4 expressions in PDAC were significant prognostic factors for early tumor recurrence (hazard risk [HR], 5.185 and 2.490, P = 0.048 and 0.009, respectively) and poor survival (HR, 11.977 and 3.202, P = 0.006 and 0.004, respectively). In addition, the interaction between CD24 and S100A4 expression status was a significant prognostic factor for poor survival (HR, 18.518, P = 0.003).
  
  
  CONCLUSIONS
  The expression of markers of EMT and metastasis in PDACs was significantly associated with pathologic features of aggressiveness. CD24 and S100A4 expressions were significant predictors of poor survival; thus, immunohistochemistry for these markers in resected specimens may help to identify PDAC patients with a poor prognosis.
authors.affiliation: From the *Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine; †Seoul National University Hospital; ‡Department of Pathology, Seoul National University College of Medicine, Seoul; §Seoul National University Bundang Hospital, Seongnam, Gyeonggi-do; ∥Department of Surgery, Seoul National University College of Medicine, Seoul; and ¶Department of Internal Medicine, Cheju Halla General Hospital, Cheju-si, Cheju-do, Korea.
authors.forename: Sang Hyub
authors.initials: SH
authors.lastname: Lee
authors.forename: Haeryoung
authors.initials: H
authors.lastname: Kim
authors.forename: Jin-Hyeok
authors.initials: JH
authors.lastname: Hwang
authors.forename: Eun
authors.initials: E
authors.lastname: Shin
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Dae Wook
authors.initials: DW
authors.lastname: Hwang
authors.forename: Jai Young
authors.initials: JY
authors.lastname: Cho
authors.forename: Yoo-Seok
authors.initials: YS
authors.lastname: Yoon
authors.forename: Ho-Seong
authors.initials: HS
authors.lastname: Han
authors.forename: Byung Hyo
authors.initials: BH
authors.lastname: Cha
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000368:Aged; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D051927:CD24 Antigen / Q000096:biosynthesis*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D003598:Cytoskeletal Proteins / Q000096:biosynthesis; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D016016:Proportional Hazards Models; D055293:Receptors, Urokinase Plasminogen Activator / Q000096:biosynthesis; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000096:biosynthesis*; D014746:Vimentin / Q000096:biosynthesis; D000099149:Ezrin
chemical_list: D014408:Biomarkers, Tumor; D051927:CD24 Antigen; D003598:Cytoskeletal Proteins; D018960:Hyaluronan Receptors; D055293:Receptors, Urokinase Plasminogen Activator; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; D014746:Vimentin; D000099149:Ezrin; C077591:S100A4 protein, human