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Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: frequent allelic loss on chromosome 11p and alterations in the APC/beta-catenin pathway.

Authors: Abraham, SC  Wu, TT  Hruban, RH  Lee, JH  Yeo, CJ  Conlon, K  Brennan, M  Cameron, JL  Klimstra, DS 
Citation: Abraham SC, etal., Am J Pathol. 2002 Mar;160(3):953-62.
Pubmed: (View Article at PubMed) PMID:11891193

Acinar cell carcinomas (ACCs) are rare malignant tumors of the exocrine pancreas. The specific molecular alterations that characterize ACCs have not yet been elucidated. ACCs are morphologically and genetically distinct from the more common pancreatic ductal adenocarcinomas. Instead, the morphological, immunohistochemical, and clinical features of ACCs overlap with those of another rare pancreatic neoplasm, pancreatoblastoma. We have recently demonstrated a high frequency of allelic loss on chromosome arm 11p and mutations in the APC/beta-catenin pathway in pancreatoblastomas, suggesting that similar alterations might also play a role in the pathogenesis of some ACCs. We analyzed a series of 21 ACCs for somatic alterations in the APC/beta-catenin pathway and for allelic loss on chromosome 11p. In addition, we evaluated the ACCs for alterations in p53 and Dpc4 expression using immunohistochemistry, and for microsatellite instability (MSI) using polymerase chain amplification of a panel of microsatellite markers. Allelic loss on chromosome 11p was the most common genetic alteration in ACCs, present in 50% (6 of 12 informative cases). Molecular alterations in the APC/beta-catenin pathway were detected in 23.5% (4 of 17) of the carcinomas, including one ACC with an activating mutation of the beta-catenin oncogene and three ACCs with truncating APC mutations. One ACC (1 of 13, 7.6%) showed allelic shifts in four of the five markers tested (MSI-high), two (15.4%) showed an allelic shift in only one of the five markers tested (MSI-low), and no shifts were detected in the remaining 10 cases. The MSI-high ACC showed medullary histological features. In contrast, no loss of Dpc4 protein expression or p53 accumulation was detected. These results indicate that ACCs are genetically distinct from pancreatic ductal adenocarcinomas, but some cases contain genetic alterations common to histologically similar pancreatoblastomas.


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CRRD Object Information
CRRD ID: 2317200
Created: 2010-03-19
Species: All species
Last Modified: 2010-03-19
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.