Solid pseudopapillary neoplasms of the pancreas are associated with FLI-1 expression, but not with EWS/FLI-1 translocation

Tiemann, Katharina; Kosmahl, Markus; Ohlendorf, Julia; Krams, Matthias; Klöppel, Günter

doi:10.1038/modpathol.3800664

Cited by 30 publications

(20 citation statements)

References 15 publications

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“…One study of 30 solid pseudopapillary neoplasms and an additional case report did not show any chromosomal loss or gain. 11,17 Interestingly, all these cases had benign features. Using the more sensitive array CGH method, a recent report demonstrated loss of heterozygosity for HRAS in chromosome band 11p15.5 and a less significant loss of the short arm of chromosome 16.…”

Section: Discussionmentioning

confidence: 93%

“…In addition to b-catenin mutations, an EWS/FLI-1 fusion transcript, t(11;22) (q24;q12), has been reported in a pediatric solid pseudopapillary neoplasm. 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.…”

Section: Discussionmentioning

confidence: 99%

“…3,6,[8][9][10][11] Various chromosomal abnormalities have also been reported, primarily using cytogenetic techniques. [12][13][14][15][16] Two studies using comparative genomic hybridization (CGH) found no chromosomal gains or losses, 11,17 while in another study of one case using the more sensitive array CGH technique, two alterations were detected: loss of heterozygosity for HRAS in chromosome band 11p15.5 and a less significant loss of the short arm of chromosome 16. 13 Unlike ductal adenocarcinomas of the pancreas, solid pseudopapillary neoplasms do not typically have KRAS, p16, DPC4 or p53 gene alterations but do harbor mutations in the APC/b-catenin pathway with overexpression of b-catenin and cyclin D1.…”

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

et al. 2008

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Solid pseudopapillary neoplasms of the pancreas are low-grade malignancies, but their biological behavior cannot be stratified solely on the basis of histopathologic criteria. Aside from mutations in b-catenin and lack of genetic changes common to pancreatic ductal adenocarcinomas, little is known about the chromosomal alterations in solid pseudopapillary neoplasms. We applied array comparative genomic hybridization to a series of 12 patients. The average age was 31 years (range 12-52 years) with 10 female and 2 male patients. The average tumor size was 7.3 cm (range 2-24 cm) with five lesions greater than 5 cm. All cases had 'bland' cytology without significant pleomorphism or high nuclear grade, but seven cases demonstrated at least one of these potentially aggressive histopathologic features: size 45 cm, tumor necrosis, lymphovascular invasion, perineural invasion and peripancreatic invasion. Clinically, one lesion demonstrated aggressive behavior. By array comparative genomic hybridization, chromosomal losses and/or gains were identified in eight cases; five cases had multiple (five or more) alterations. The most common alterations were gains at 13q, 17q, 1q and 8q. Six of the seven cases with at least one aggressive feature had genetic alterations, while only two cases without adverse features had genetic alterations (P ¼ 0.024). The single clinically aggressive tumor exhibited seven chromosomal gains and four aggressive histopathologic features. Our study demonstrates that genetic alterations detected by array comparative genomic hybridization are common in solid pseudopapillary neoplasms of the pancreas. Additional study and longer follow-up are needed to determine if these genetic abnormalities could help predict clinical behavior in these neoplasms.

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Section: Discussionmentioning

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

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

et al. 2008

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“…27 The observed changes are not associated with gross chromosomal aberrations of this region, because such alterations were ruled out by comparative genomic hybridization of solid pseudopapillary neoplasms. 28 However, despite the absence of gross chromosome abnormalities, this chromosomal area seems to be vulnerable to distinct genetic changes in solid pseudopapillary neoplasms, because it harbors a number of genes whose proteins are frequently found to be overexpressed. These proteins include cyclin D1, FLI-1, progesterone receptor and CD56.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2007

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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;

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“…Microscopically, the tumor cells in 'solid' areas are uniform, arranged in sheets and cords around fibrovascular septa; whereas those in 'pseudopapillary' areas show degenerative changes in the cells away from the vasculature. [4][5][6][7][8] Despite its characteristic microscopic appearance and recent studies of this type of tumor for molecular changes, 9 the immunophenotype of markers is not specific and does not define a line of differentiation corresponding to any normal pancreatic cell type.…”

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Loss of cell-adhesion molecule complexes in solid pseudopapillary tumor of pancreas

et al. 2007

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Solid pseudopapillary tumor of pancreas (SPT) is a rare neoplasm that occurs most often in young females with the two distinct features, the 'solid-cystic' gross appearance, and the 'solid-pseudopapillary' microscopic pattern. It has been reported that almost all SPT tumors contain a mutation in the b-catenin gene; however, the histogenetic origin of this tumor remains largely a mystery. E-cadherin is a cell adhesion molecule that links to catenins to form cell adhesion junctions, which is associated with the cytoskeleton formation. In this study, we examined the expression of E-cadherin and b-catenin from SPT in an attempt to determine the molecular basis for the unusual morphology of this tumor. Nine cases of SPT were retrieved from Surgical Pathologic Archives of three institutions, including one male and eight females. H&E slides of each case were reviewed to confirm the diagnosis. The b-catenin gene was sequenced in one case. E-cadherin and b-catenin immunostains, were performed on all nine cases. Sequencing analysis on one case showed a point mutation of the b-catenin gene, confirming previous findings that almost all SPT tumors contain mutation in the b-catenin gene. Immunostains showed that, in both solid and pseudopapillary areas, all the tumor cells lost expression of E-cadherin, and bcatenin nuclear expression was observed in all cases. Our findings suggest that loss of cytoplasmic b-catenin protein in the cell adhesion complex due to b-catenin gene mutation, results in instability of the complex, loss of E-cadherin in cell membrane, and eventually dissociation of the tumor cells to form the pseudopapillary pattern. Modern Pathology (2007) 20, 509-513.

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Solid pseudopapillary neoplasms of the pancreas are associated with FLI-1 expression, but not with EWS/FLI-1 translocation

Cited by 30 publications

References 15 publications

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

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

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

Loss of cell-adhesion molecule complexes in solid pseudopapillary tumor of pancreas

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