| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Short Communication |
From the Division of Gastrointestinal/Liver Pathology, the
Departments of Pathology*
and
Surgery,
The Johns Hopkins University School
of Medicine, Baltimore, Maryland; the Department of
Pathology,
Memorial Sloan-Kettering Cancer
Center, New York, New York; and the Department of
Pathology,
Children’s Hospital and Regional
Medical Center, Seattle, Washington
Pancreatoblastomas are unusual malignant neoplasms of the pediatric pancreas that may also rarely affect adults. The molecular pathogenesis of pancreatoblastomas is unknown. They are clinicopathologically distinct from adult pancreatic ductal adenocarcinomas, but their occasional occurrence in patients with Beckwith-Wiedemann syndrome and the case presented here of a pancreatoblastoma in an adult patient with familial adenomatous polyposis (FAP) suggests that they might bear a genetic similarity to other infantile embryonal tumors such as hepatoblastomas. We analyzed a series of nine pancreatoblastomas for mutations common to other embryonal malignancies including somatic alterations in the adenomatous polyposis coli (APC)/ß-catenin pathway and chromosome 11p, using immunohistochemistry for ß-catenin, 5q and 11p allelic loss assays, and direct DNA sequencing of exon 3 of the ß-catenin gene and the mutation cluster region of the APC gene. In addition, we analyzed the pancreatoblastomas for alterations found in adult-type pancreatic ductal adenocarcinomas including mutations in the K-ras oncogene and the p53 and DPC4 tumor suppressor genes, using direct DNA sequencing of exon 1 of K-ras and immunohistochemistry for p53 and Dpc4. Allelic loss on chromosome 11p was the most common genetic alteration in pancreatoblastomas, present in 86% (six of seven informative cases). Molecular alterations in the APC/ß-catenin pathway were detected in 67% (six of nine), including five neoplasms with activating mutations of the ß-catenin oncogene and the one FAP-associated tumor with biallelic APC inactivation (germline truncating mutation combined with loss of the wild-type allele); seven neoplasms showed abnormal nuclear accumulation of ß-catenin protein. In contrast, loss of Dpc4 protein expression was present in only two cases (one diffuse and one focal), and no alterations in the K-ras gene or p53 expression were detected. Our findings indicate that pancreatoblastomas are genetically distinct from the more common pancreatic ductal adenocarcinomas, but bear a close molecular pathogenesis to hepatoblastomas. In addition, pancreatoblastoma may represent an extracolonic manifestation of FAP.
This article has been cited by other articles:
 |
|
 |
|
  A. M. Bellizzi and W. L. Frankel Pancreatic Pathology: A Practical Review Lab Med, July 1, 2009; 40(7): 417 - 426. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. B. Halberg, X. Chen, J. M. Amos-Landgraf, A. White, K. Rasmussen, L. Clipson, C. Pasch, R. Sullivan, H. C. Pitot, and W. F. Dove The Pleiotropic Phenotype of Apc Mutations in the Mouse: Allele Specificity and Effects of the Genetic Background Genetics, September 1, 2008; 180(1): 601 - 609. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Romero, M. Iglesias, C. P.H. Vary, and M. Quintanilla Functional blockade of Smad4 leads to a decrease in {beta}-catenin levels and signaling activity in human pancreatic carcinoma cells Carcinogenesis, May 1, 2008; 29(5): 1070 - 1076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. F. Hezel, A. C. Kimmelman, B. Z. Stanger, N. Bardeesy, and R. A. DePinho Genetics and biology of pancreatic ductal adenocarcinoma. Genes & Dev., May 15, 2006; 20(10): 1218 - 1249. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Tang, V. Katuri, R. Srinivasan, F. Fogt, R. Redman, G. Anand, A. Said, T. Fishbein, M. Zasloff, E. P. Reddy, et al. Transforming Growth Factor-{beta} Suppresses Nonmetastatic Colon Cancer through Smad4 and Adaptor Protein ELF at an Early Stage of Tumorigenesis Cancer Res., May 15, 2005; 65(10): 4228 - 4237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Buda and M. Pignatelli Genetics - cellular basis: Advances in colorectal cancer Br. Med. Bull., December 1, 2002; 64(1): 45 - 58. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. C. Abraham, D. S. Klimstra, R. E. Wilentz, C. J. Yeo, K. Conlon, M. Brennan, J. L. Cameron, T.-T. Wu, and R. H. Hruban Solid-Pseudopapillary Tumors of the Pancreas Are Genetically Distinct from Pancreatic Ductal Adenocarcinomas and Almost Always Harbor {beta}-catenin Mutations Am. J. Pathol., April 1, 2002; 160(4): 1361 - 1369. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. Sullivan, S. C. Abraham, R. H. Hruban, B. Bachtiary, G. Breitenecker, E. Selzer, G. Oberhuber, and J. T. Beranek Beckwith-Wiedemann Syndrome, Pancreatoblastoma, and the Wnt Signaling Pathway Am. J. Pathol., April 1, 2002; 160(4): 1541 - 1542. [Full Text] [PDF]
|
|
|
|
|
|
S. C. Abraham, T.-T. Wu, R. H. Hruban, J.-H. Lee, C. J. Yeo, K. Conlon, M. Brennan, J. L. Cameron, and D. S. Klimstra Genetic and Immunohistochemical Analysis of Pancreatic Acinar Cell Carcinoma : Frequent Allelic Loss on Chromosome 11p and Alterations in the APC/{beta}-Catenin Pathway Am. J. Pathol., March 1, 2002; 160(3): 953 - 962. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
