Solid pseudopapillary neoplasms of the pancreas show an interruption of the Wnt-signaling pathway and express gene products of 11q.
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.
Tiemann
Katharina
K
Department of Pathology, University of Kiel, Kiel, Germany. k.peters@path.uni-kiel.de
Heitling
Ulrike
U
Kosmahl
Markus
M
Klöppel
Günter
G
D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000235:genetics; D019002:CD56 Antigen / Q000032:analysis; D049109:Cell Proliferation; D002648:Child; D002880:Chromosomes, Human, Pair 11; D056741:Cyclin D; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000032:analysis; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000032:analysis; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000032:analysis; D016213:Cyclins / Q000032:analysis; D003937:Diagnosis, Differential; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D018358:Neuroendocrine Tumors / Q000737:chemistry* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000175:diagnosis / Q000235:genetics / Q000473:pathology; D010766:Phosphorylation; D016160:Retinoblastoma Protein / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D051153:Wnt Proteins / Q000032:analysis* / Q000235:genetics; D051176:beta Catenin / Q000032:analysis
D014408:Biomarkers, Tumor; D019002:CD56 Antigen; C493956:CDKN1A protein, human; C495270:CTNNB1 protein, human; D056741:Cyclin D; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016160:Retinoblastoma Protein; D051153:Wnt Proteins; D051176:beta Catenin; D050760:Cyclin-Dependent Kinase Inhibitor p27