title: Gene expression changes associated with the progression of intraductal papillary mucinous neoplasms.
abstract: OBJECTIVE
  The diagnosis of high-grade intraductal papillary mucinous neoplasm (IPMN) is difficult to distinguish from low-grade IPMN. The aim of this study was to identify potential markers for the discrimination of high-grade and invasive (HgInv) IPMN from low- and moderate-grade dysplasia IPMN.
  
  
  METHODS
  Laser capture microdissection was used to isolate distinct foci of low-grade, moderate-grade, high-grade, and invasive IPMN from paraffin-embedded archival tissue from 14 patients who underwent resection for IPMN. Most samples included multiple grades in the same specimen. Affymetrix Human Exon microarrays were used to compare low- and moderate-grade dysplasia IPMN with HgInv IPMN.
  
  
  RESULTS
  Sixty-two genes were identified as showing significant changes in expression (P ≤ 0.05 and a 2-fold cutoff), including up-regulation of 41 in HgInv IPMN. Changes in gene expression are associated with biological processes related to malignant behavior including cell motion, cell proliferation, response to hypoxia, and epithelial-to-mesenchymal transition. In addition, altered signaling in several transforming growth factor β-related pathways was exhibited in the progression of IPMN to malignancy.
  
  
  CONCLUSIONS
  This study identifies a set of genes associated with the progression of IPMN to malignancy. These genes are potential markers that could be used to identify IPMN requiring surgical resection.
authors.affiliation: General Surgery, Beaumont Health System, Royal Oak, MI, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Jury
authors.forename: Bryan J
authors.initials: BJ
authors.lastname: Thibodeau
authors.forename: Laura E
authors.initials: LE
authors.lastname: Fortier
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Geddes
authors.forename: Samreen
authors.initials: S
authors.lastname: Ahmed
authors.forename: Barbara L
authors.initials: BL
authors.lastname: Pruetz
authors.forename: Maryam A
authors.initials: MA
authors.lastname: Farinola
authors.forename: George D
authors.initials: GD
authors.lastname: Wilson
mesh_terms: D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D000231:Adenocarcinoma, Papillary / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D020869:Gene Expression Profiling; D005819:Genetic Markers; D006801:Humans; D061346:Laser Capture Microdissection; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011230:Precancerous Conditions / Q000235:genetics* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D005819:Genetic Markers