Document Detail

Solid pseudopapillary neoplasms of the pancreas show an interruption of the Wnt-signaling pathway and express gene products of 11q.
MedLine Citation:
PMID:  17632456     Owner:  NLM     Status:  MEDLINE    
Solid pseudopapillary neoplasms of the pancreas almost consistently show a beta-catenin mutation activating the Wnt-signaling pathway, resulting in overexpression of cyclin D1, but not in overt malignancy of this tumor. Besides cyclin D1, a set of markers (ie FLI-1, CD56 and progesterone receptor), whose genes map to chromosome 11q, are frequently expressed in solid pseudopapillary neoplasms. Chromosome 11q is a region that is also often affected in pancreatic neuroendocrine tumors. This immunohistochemical study was undertaken to gain insights into the downstream regulation of the Wnt-signaling pathway and the significance of overexpressed gene products belonging to chromosome 11q for the tumorigenesis in solid pseudopapillary neoplasms. Fourteen solid pseudopapillary neoplasms were analyzed for the expression of cyclin-dependent kinase inhibitors p21, p27, p16 and hyperphosphorylated retinoblastoma (pRb) proteins. In an extended series of 93 solid pseudopapillary neoplasms, beta-catenin, cyclin D1, FLI-1 and CD56 expression was examined and compared with that in 22 pancreatic neuroendocrine tumors. Solid pseudopapillary neoplasms (98%) showed aberrant expression of beta-catenin with a concomitant cyclin D1 expression in 69% of the cases, but no expression of pRb (0%) was found. p27 and p21 were expressed in 100% (14/14) and 86% (12/14) of the cases, but only 2/14 (14%) were positive for p16. FLI-1 was expressed in 63% of solid pseudopapillary neoplasms, but only in 1/22 pancreatic neuroendocrine tumors (5%), cyclin D1 expression was present in 14% of the latter. We conclude that in solid pseudopapillary neoplasms the activated Wnt-signaling pathway is disrupted, and that p21 and p27 are contributing to this fact by blocking of the hyperphosphorylation of the Rb protein, thus causing the very low proliferation rate characterizing the solid pseudopapillary neoplasms. The accumulation of high expression of proteins whose genes are located on chromosome 11q is characteristic of solid pseudopapillary neoplasms, but not of pancreatic neuroendocrine tumors.
Katharina Tiemann; Ulrike Heitling; Markus Kosmahl; Günter Klöppel
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Publication Detail:
Type:  Comparative Study; Journal Article     Date:  2007-07-13
Journal Detail:
Title:  Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc     Volume:  20     ISSN:  0893-3952     ISO Abbreviation:  Mod. Pathol.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-08-16     Completed Date:  2007-10-25     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8806605     Medline TA:  Mod Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  955-60     Citation Subset:  IM    
Department of Pathology, University of Kiel, Kiel, Germany.
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MeSH Terms
Antigens, CD56 / analysis
Cell Proliferation
Chromosomes, Human, Pair 11*
Cyclin D
Cyclin-Dependent Kinase Inhibitor p16 / analysis
Cyclin-Dependent Kinase Inhibitor p21 / analysis
Cyclin-Dependent Kinase Inhibitor p27 / analysis
Cyclins / analysis
Diagnosis, Differential
Gene Expression Regulation, Neoplastic*
Middle Aged
Neuroendocrine Tumors / chemistry*,  diagnosis,  genetics,  pathology
Pancreatic Neoplasms / chemistry*,  diagnosis,  genetics,  pathology
Retinoblastoma Protein / metabolism
Signal Transduction* / genetics
Tumor Markers, Biological / analysis*,  genetics
Wnt Proteins / analysis*,  genetics
beta Catenin / analysis
Reg. No./Substance:
0/Antigens, CD56; 0/CDKN1A protein, human; 0/CTNNB1 protein, human; 0/Cyclin D; 0/Cyclin-Dependent Kinase Inhibitor p16; 0/Cyclin-Dependent Kinase Inhibitor p21; 0/Cyclins; 0/Retinoblastoma Protein; 0/Tumor Markers, Biological; 0/Wnt Proteins; 0/beta Catenin; 147604-94-2/Cyclin-Dependent Kinase Inhibitor p27

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