Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: Frequent allelic loss on chromosome 11p and alterations in the APC/β-catenin pathway Journal Article
| Authors: | Abraham, S. C.; Wu, T. T.; Hruban, R. H.; Lee, J. H.; Yeo, C. J.; Conlon, K.; Brennan, M.; Cameron, J. L.; Klimstra, D. S. |
| Article Title: | Genetic and immunohistochemical analysis of pancreatic acinar cell carcinoma: Frequent allelic loss on chromosome 11p and alterations in the APC/β-catenin pathway |
| Abstract: | 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/β-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/β-catenin pathway and for allelic loss on chromosome lip. 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 lip was the most common genetic alteration in ACCs, present in 50% (6 of 12 informative cases). Molecular alterations in the APC/β-catenin pathway were detected in 23.5% (4 of 17) of the carcinomas, including one ACC with an activating mutation of the β-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. |
| Keywords: | immunohistochemistry; signal transduction; adolescent; adult; clinical article; human tissue; aged; child, preschool; middle aged; gene mutation; mutation; pancreatic neoplasms; genetic analysis; protein p53; pancreas carcinoma; microsatellite instability; gene loss; pancreas adenocarcinoma; trans-activators; heterozygosity loss; loss of heterozygosity; acinar cell carcinoma; carcinoma, acinar cell; beta catenin; chromosomes, human, pair 11; adenomatous polyposis coli protein; apc protein; genes, tumor suppressor; cytoskeletal proteins; chromosomes, human, pair 5; chromosome 11p; blastoma; humans; human; male; female; priority journal; article |
| Journal Title: | American Journal of Pathology |
| Volume: | 160 |
| Issue: | 3 |
| ISSN: | 0002-9440 |
| Publisher: | Elsevier Science, Inc. |
| Date Published: | 2002-03-01 |
| Start Page: | 953 |
| End Page: | 962 |
| Language: | English |
| PUBMED: | 11891193 |
| PROVIDER: | scopus |
| PMCID: | PMC1867188 |
| DOI: | 10.1016/S0002-9440(10)64917-6 |
| DOI/URL: | |
| Notes: | Export Date: 14 November 2014 -- Source: Scopus |
Altmetric
Citation Impact
BMJ Impact Analytics
Related MSK Work