Solid pseudopapillary neoplasms of the pancreas show an interruption of the Wnt-signaling pathway and express gene products of 11q

Abstract

Solid pseudopapillary neoplasms of the pancreas almost consistently show a b-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, b-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 b-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. Modern Pathology (2007) 20, 955-960;

Array comparative genomic hybridization analysis of solid pseudopapillary neoplasms of the pancreas

“…14 Subsequent papers showed that although FLI-1 is overexpressed in solid pseudopapillary neoplasms, 17 it is more likely due to a genetic alteration involving the long arm of chromosome 11 rather than an EWS-FLI-1 transcript. 20 Interestingly, two of our patients showed loss of 11q22.3, and one showed a gain at 11q13.5-q14, suggesting a role for changes in chromosome 11q during the development of solid pseudopapillary neoplasms.…”

Large, clear cytoplasmic vacuolation

“…Recent studies have also highlighted the genetic and immunophenotypic expression patterns of b-catenin and E-cadherin in SPN and PEN. [29][30][31] In conclusion, we wish to highlight that large, clear cytoplasmic vacuoles can serve as a critical clue with which to distinguish SPN from PEN in diagnostically challenging cases. In such cases, adequate samples should be obtained to perform supportive ancillary studies as needed.…”

Gastrointestinal, Pancreatic and Hepatic Malignancies in Children

“…The accumulation of protein products of chromosome 11q genes, such as cyclin D1, CD56, and FLI-1, is also characteristic [ 44 ]. Allelic loss on chromosome 5q22.1 was frequently found by Min Kim et al [ 42 ].…”