title: Anterior gradient 2 and mucin 4 expression mirrors tumor cell differentiation in pancreatic adenocarcinomas, but aberrant anterior gradient 2 expression predicts worse patient outcome in poorly differentiated tumors.
abstract: OBJECTIVE
  This study aimed to determine anterior gradient 2 (AGR2) expression in biopsies from pancreatic ductal adenocarcinomas (PDACs) and to evaluate AGR2 as a potential independent prognostic factor.
  
  
  METHODS
  Tissue sample sections from a cohort of 135 consecutive surgically resectable PDACs were subjected to semiquantitative immunohistochemical analysis of AGR2 and mucin 4 (MUC4) expression.
  
  
  RESULTS
  Anterior gradient 2 was over-expressed in PDAC compared with normal ductal cells. Since tumor lesions of PDAC are heterogeneous and constitute structures with various differentiation states, expression of both AGR2 and MUC4 was evaluated in each separate component. Expression levels of both proteins reflected the degree of tumor differentiation. Generally, well differentiated regions of tumor lesions expressed high levels of both proteins, moderately differentiated regions showed less AGR2 and MUC4, and poorly differentiated structures showed only weak positivity or were entirely negative. Of particular interest were occasional cases of strong AGR2 expression in high-grade tumors, where elevated protein levels were associated with shorter patient survival.
  
  
  CONCLUSIONS
  Anterior gradient 2 and MUC4 reflect the level of differentiation of PDACs. However, in less differentiated tumors, aberrantly elevated AGR2 expression predicts poor patient outcome.
authors.affiliation: From the *Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute; †First Department of Pathological Anatomy, St Anne's University Hospital, Medical Faculty of Masaryk University; ‡Department of Complex Oncology Care, Masaryk Memorial Cancer Institute; §Department of Mathematics and Statistics, Faculty of Science, Masaryk University; and ∥Department of Surgery, University Hospital Brno, Medical Faculty of Masaryk University, Brno, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Brychtova
authors.forename: Marketa
authors.initials: M
authors.lastname: Hermanova
authors.forename: Petr
authors.initials: P
authors.lastname: Karasek
authors.forename: Jiri
authors.initials: J
authors.lastname: Lenz
authors.forename: Iveta
authors.initials: I
authors.lastname: Selingerova
authors.forename: Borivoj
authors.initials: B
authors.lastname: Vojtesek
authors.forename: Zdenek
authors.initials: Z
authors.lastname: Kala
authors.forename: Roman
authors.initials: R
authors.lastname: Hrstka
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D055264:Mucin-4 / Q000378:metabolism; D009088:Mucoproteins; D015513:Oncogene Proteins; D017063:Outcome Assessment, Health Care / Q000706:statistics & numerical data; D010180:Pancreatectomy; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D011506:Proteins / Q000378:metabolism*
chemical_list: C502296:AGR2 protein, human; C524658:MUC4 protein, human; D055264:Mucin-4; D009088:Mucoproteins; D015513:Oncogene Proteins; D011506:Proteins