title: Histologic, immunohistochemical, and molecular classification of 52 IPMNs of the pancreas.
abstract: BACKGROUND
  Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas account for approximately 5% of pancreatic neoplasms. Prognosis is superior to that of pancreatic invasive ductal carcinoma. IPMNs reveal a variety of epithelial linings expressing different mucin staining patterns and may progress along different oncogenic pathways.
  
  
  METHODS
  Fifty-two IPMNs were studied for expression of MUC1, MUC2, p16, p21, HER2, cyclin D1, and p53 protein and for mutations in K-ras, HER2, p53, EGFR, and BRAF genes. The cases were evaluated for dysplasia, presence of invasion, and morphology of lining epithelium.
  
  
  RESULTS
  Twenty-six IPMNs appeared intestinal (IN). Five were low, 12 moderate, and 9 high grade. K-ras mutations were found in 15, EGFR mutations in 2, and BRAF mutation in 1. Seven cases were pancreaticobiliary (PB) and all showed moderate to high-grade dysplasia. Six K-ras mutations and 2 p53 mutations were found in PB tumors. p53 mutations were in cases with high-grade dysplasia. Nineteen IPMNs demonstrated a gastric foveolar (GF) pattern. The majority of GF cases had low or moderate dysplasia. Sixteen revealed K-ras mutations and 1 case each demonstrated a HER2 or p53 mutation. Five IPMNs revealed invasive adenocarcinoma, including a colloid carcinoma from an IN type epithelium.
  
  
  CONCLUSIONS
  IN pattern IPMNs were the most common. Mixed histology was common. K-ras mutations were most common, but did not correlate with dysplasia. p53 mutations were seen in 6% of cases (only in GF and PB subtypes). A HER2 mutation was found in a GF IPMN. EGFR and BRAF mutations were restricted to IN IPMNs. These findings suggest the possibility of alternate pathways for carcinogenesis between epithelial subtypes of IPMNs.
authors.affiliation: Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Chadwick
authors.forename: Carlynn
authors.initials: C
authors.lastname: Willmore-Payne
authors.forename: Sheryl
authors.initials: S
authors.lastname: Tripp
authors.forename: Lester J
authors.initials: LJ
authors.lastname: Layfield
authors.forename: Sharon
authors.initials: S
authors.lastname: Hirschowitz
authors.forename: Joseph
authors.initials: J
authors.lastname: Holden
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D002965:Classification; D004847:Epithelial Cells / Q000737:chemistry / Q000473:pathology; D004848:Epithelium / Q000737:chemistry / Q000473:pathology*; D020869:Gene Expression Profiling; D052138:Genes, Neoplasm; D006801:Humans; D007150:Immunohistochemistry; D007414:Intestinal Neoplasms / Q000473:pathology; D009077:Mucins / Q000737:chemistry; D009154:Mutation; D009363:Neoplasm Proteins / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D009077:Mucins; D009363:Neoplasm Proteins