A new molecular variant of desmoplastic small round cell tumor: significance of WT1 immunostaining in this entity

Murphy, Anna V.; Bishop, Karen; Pereira, Carlos Augusto; Chilton‐MacNeill, Susan; Ho, Michael; Zieleńska, Maria; Thorner, Paul

doi:10.1016/j.humpath.2008.04.019

Cited by 67 publications

(52 citation statements)

References 36 publications

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“…Originally, described as a predominantly intra-abdominal tumor, a broader distribution has emerged gradually that includes pleura [61] and tunica vaginalis [62]. Extraserous location has been occasionally reported, including parotid gland [63], posterior cranial fossa [64], central nervous system [65], bone and soft tissue [66][67][68], ovary [69], pancreas [70], and kidney [71,72].…”

Section: Desmoplastic Small Round Cell Tumormentioning

confidence: 99%

Soft tissue tumors associated with EWSR1 translocation

2009

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The Ewing sarcoma breakpoint region 1 (EWSR1; also known as EWS) represents one of the most commonly involved genes in sarcoma translocations. In fact, it is involved in a broad variety of mesenchymal lesions which includes Ewing's sarcoma/peripheral neuroectodermal tumor, desmoplastic small round cell tumor,clear cell sarcoma, angiomatoid fibrous histiocytoma, extraskeletal myxoid chondrosarcoma, and a subset of myxoid liposarcoma. The fusion products between EWSR1 and partners usually results in fusion of the N-terminal transcription-activating domain of EWSR1 and the C-terminal DNA-binding domain of the fusion partner, eventually generating novel transcription factors. EWSR1 rearrangement can be visualized by the means of fluorescence in situ hybridization (FISH). As soft tissue sarcomas represent a diagnostically challenging group, FISH analysis is an extremely useful confirmatory diagnostic tool. However, as in most instances a split-apart approach is used, the results of molecular genetics must be evaluated in context with morphology.

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Section: Desmoplastic Small Round Cell Tumormentioning

confidence: 99%

Soft tissue tumors associated with EWSR1 translocation

2009

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“…It has been shown that the EWS-WT1 chimera leads to the transcription of a number of the target genes involved in proliferation, survival and invasion, including PDGFRA [2]. Furthermore, it has been reported that a number of fusion transcription variants (including full-length WT1) may give rise to an atypical staining pattern using antibody against the C terminal of WT1 [3] that may complicate an immunophenotypical diagnosis. Somatic MET and PIK3CA mutations have been identified [4], and there have been reports of the deregulation of epigenetic modifications, such as the expression of lysine specific demethylase (LSD1) [5], and the loss of INI [6] and SMARCA4 [7], thus suggesting that the SWI/SNF chromatin remodelling complex may play a role in DSRCTs.…”

Section: Introductionmentioning

confidence: 99%

New transcriptional-based insights into the pathogenesis of desmoplastic small round cell tumors (DSRCTs)

et al. 2017

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To gain new insights into desmoplastic small round cell tumors (DSRCTs) by means of gene expression profiling (GEP). Formalin-fixed, paraffin-embedded surgical specimens obtained from seven pretreated DSRCT patients were interrogated using GEP complemented by immunohistochemistry, a cancer stem cell array, and miRNA in situ hybridisation, including the combined chimera modules miRNA-200/ZEB1 and miRNA-34/SLUG. The chimera modules divided the cases into three classes that respectively recapitulated the traits of mesenchymal epithelial reverse transition (MErT), epithelial mesenchymal transition (EMT), and hybrid/partial EMT. This indicates a close correlation between the reprogramming governed by EMT regulators and DSRCT biology, which was further confirmed by miRNA-21 and is consistent with the broad morphological spectrum of DSRCTs. Starting from the miRNA-200/ZEB1 axis, we also found that DSRCTs carry a signature of immunological ignorance that is not responsive to PD-L1 blockade. Evidence that the up-regulation of miRNA-200 and E-cadherin, and quite a high level of miRNA-21 expression segregate with the MErT supports the idea that, in addition to the hybrid/partial state, MErT is also enriched in stemness: the androgen-positive cases, whose stemness traits were confirmed by stem cell arrays, all fell into these two classes. Our findings also confirmed that tumoral cell PDGFRA expression correlates with desmoplasia, and demonstrated the co-expression of PDGFRA and ISLR/Meflin, another marker of pluripotency. Despite the limited number of cases, these findings provide unexpectedly relevant information concerning the pathogenesis of DSRCTs, and prove the validity of miRNA-based chimera circuit modelling in the clinico-pathological setting.

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“…Several fusion partners, including CTNNB1 [6,7], CHCHD7 [4], LIFR [6,8], and TCEA1 [4,5] fused to PLAG1 as well as NFIB [11], FHIT [12], and WIF1 [13] fused to HMGA2, were identified by using reverse transcription (RT)-polymerase chain reaction (PCR), fluorescence in situ hybridization (FISH), or chromogenic in situ hybridization (CISH) performed on fresh tumor tissue specimens. Some tumorspecific genetic alterations including chromosomal translocations can also be specifically identified immunohistochemically via the proteins translated from the fusion gene transcripts [14][15][16][17]. The PLAG1 protein is a nuclear oncoprotein that functions as a DNA-binding transcription factor and is overexpressed not only in pleomorphic adenoma but also in lipoblastoma [18], hepatoblastoma [19], lymphocytic leukemia [20], and pediatric gastrointestinal stromal tumors [21].…”

Section: Introductionmentioning

confidence: 99%

PLAG1 expression in cutaneous mixed tumors: an immunohistochemical and molecular genetic study

2011

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Cutaneous mixed tumors, also known as chondroid syringomas, are benign cutaneous adnexal tumors that exhibit remarkable histopathological similarities to pleomorphic adenoma of the salivary gland. Thus far, there is little information on the genetic profiles of cutaneous mixed tumors, although specific genetic aberrations including fusion genes involving PLAG1 and HMGA2 have been demonstrated in pleomorphic adenomas. In the present study, we conducted an immunohistochemical evaluation of PLAG1 and a reverse transcription-polymerase chain reaction (RT-PCR) assay to detect fusion gene transcripts associated with pleomorphic adenoma, including the CTNNB1-PLAG1, LIFR-PLAG1, CHCHD7-PLAG1, TCEA1-PLAG1, HMGA2-FHIT, HMGA2-NFIB, and HMGA2-WIF1 fusion transcripts; this was performed using formalin-fixed paraffin-embedded tumor tissue specimens of 16 cutaneous mixed tumors including one sample with an adenocarcinoma component. All 16 cutaneous mixed tumors were immunoreactive to PLAG1, which was predominantly expressed in cells with myoepithelial or chondroid differentiation accounting for >80% of cells, whereas PLAG1 expression in glandular or squamous tumor cells was restricted to <20% of cells. The carcinoma component in the mixed tumor was also positive for PLAG1. On the other hand, all eight cutaneous adnexal tumors other than the mixed tumor were negative for PLAG1. In RT-PCR analysis, no fusion gene transcripts involving PLAG1 or HMGA2 were identified in any of the cases. Concordant with previous studies, our results support the close relationship between cutaneous mixed tumors and pleomorphic adenomas of the salivary gland. However, the mechanism of PLAG1 expression in cutaneous mixed tumors appears to be possibly different from that of pleomorphic adenomas.

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A new molecular variant of desmoplastic small round cell tumor: significance of WT1 immunostaining in this entity

Cited by 67 publications

References 36 publications

Soft tissue tumors associated with EWSR1 translocation

Soft tissue tumors associated with EWSR1 translocation

New transcriptional-based insights into the pathogenesis of desmoplastic small round cell tumors (DSRCTs)

PLAG1 expression in cutaneous mixed tumors: an immunohistochemical and molecular genetic study

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