Histologic, immunohistochemical, and molecular classification of 52 IPMNs of the pancreas.
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.
Chadwick
Barbara
B
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
Willmore-Payne
Carlynn
C
Tripp
Sheryl
S
Layfield
Lester J
LJ
Hirschowitz
Sharon
S
Holden
Joseph
J
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
D014408:Biomarkers, Tumor; D009077:Mucins; D009363:Neoplasm Proteins