The Experts below are selected from a list of 2043 Experts worldwide ranked by ideXlab platform
Poul H Sorensen - One of the best experts on this subject based on the ideXlab platform.
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detection of the ews wt1 gene fusion by reverse transcriptase polymerase chain reaction in the diagnosis of intra abdominal Desmoplastic small round cell Tumor
The American Journal of Surgical Pathology, 1996Co-Authors: Larry Argatoff, John X Oconnell, Joan Mathers, C B Gilks, Poul H SorensenAbstract:We report two cases of intra-abdominal Desmoplastic small round cell Tumor with characteristic clinical, histological, immunohistochemical, and ultrastructural features. Fusion of the EWS gene on chromosome 22 and the WT1 gene on chromosome 11, resulting from the chromosomal translocation t(11;22)(p13;q12), was detected by reverse transcriptase polymerase chain reaction (RT-PCR) in both cases. This translocation has been previously reported in this type of Tumor using either cytogenetic or molecular biological techniques. Tumor tissue from both cases revealed no chimeric fusion transcripts characteristic of the Ewing sarcoma family of peripheral primitive neuroectodermal Tumors or of alveolar rhabdomyosarcoma, two Tumors in the differential diagnosis of intra-abdominal Desmoplastic small round cell Tumor. This report demonstrates the utility of molecular studies as an adjunct in the diagnosis of this rare and aggressive Tumor.
William L Gerald - One of the best experts on this subject based on the ideXlab platform.
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the ews wt1 gene fusion in Desmoplastic small round cell Tumor
Seminars in Cancer Biology, 2005Co-Authors: William L Gerald, Daniel A HaberAbstract:Desmoplastic small round cell Tumor (DSRCT) is a poorly understood neoplasm with distinctive clinical, histologic and immunophenotypic features. It is associated with a novel, specific chromosomal abnormality, t(11;22)(p13;q12) that fuses EWS with WT1 leading to production of a chimeric protein with transcriptional regulatory activity. This chimeric transcription factor has unique DNA-binding properties and regulates expression of specific target genes. Several of these have been identified and their biological role characterized. The dysregulated expression of EWS-WT1 targets contribute to the malignant phenotype of DSRCT and provide valuable insight regarding the molecular mechanisms underlying the development and progression of this distinct translocation associated Tumor.
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synovial sarcoma mimicking Desmoplastic small round cell Tumor critical role for molecular diagnosis
Medical and Pediatric Oncology, 1999Co-Authors: Peter D Cole, Marc Ladanyi, Naikong V Cheung, William L Gerald, Michael P Laquaglia, Kim Kramer, Brian H KushnerAbstract:Background The identification of recently described nonrandom chromosomal defects specific for various small round-cell and spindle-cell sarcomas can eliminate diagnostic uncertainty arising from the clinical and histopathologic overlap of soft tissue neoplasms. Methods A 26-year-old man presented with bulky abdominal-pelvic disease. Immunohistochemical and molecular studies on Tumor were performed. Treatment was instituted using cycles of high-dose cyclophosphamide (4,200 mg/m2) with doxorubicin (75 mg/m2). Results Clinical findings pointed to Desmoplastic small round-cell Tumor. The Tumor was histologically undifferentiated and immunoreactive for vimentin but negative for other markers. Reverse transcriptase-polymerase chain reaction revealed the SYT/SSX2 fusion transcript of the synovial sarcoma t(X;18) chromosomal rearrangement. The high-dose chemotherapy, plus surgery, achieved a complete remission, but recurrent disease emerged 13 months from diagnosis. Conclusions This clinically unique case of synovial sarcoma highlights how the use of now readily available molecular techniques will allow more accurate appraisals of the incidence and anatomic distribution of soft tissue neoplasms—information that bears upon pathogenesis and treatment. This case confirms the utility of high-dose alkylator-based therapy for synovial sarcoma. It also demonstrates that with nonlocalized solid Tumors, the eradication of minimal residual disease remains an elusive goal. One alternative involves immunologic attack against markers derived from Tumor-specific chromosomal defects such as those found in our patient. Med. Pediatr. Oncol. 32:97–101, 1999. © 1999 Wiley-Liss, Inc.
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characterization of the genomic breakpoint and chimeric transcripts in the ews wt1 gene fusion of Desmoplastic small round cell Tumor
Proceedings of the National Academy of Sciences of the United States of America, 1995Co-Authors: William L Gerald, Juan Rosai, Marc LadanyiAbstract:Abstract Desmoplastic small round cell Tumor is a recently recognized distinctive Tumor shown to be associated with a recurrent translocation, t(11;22)(p13;q12), and rearrangement of the genes for Ewing sarcoma (EWS) and Wilms Tumor (WT1). A genomic DNA fragment containing the EWS-WT1 gene fusion has been isolated from a Desmoplastic small round cell Tumor, and the breakpoint has been characterized. The breakpoints involve the intron between EWS exons 7 and 8 and the intron between WT1 exons 7 and 8. Chimeric transcripts corresponding to the fusion gene were detected in four of six cases studied. Analysis of these transcripts show an in-frame fusion of RNA encoding the amino-terminal domain of EWS to both alternatively spliced forms of the last three zinc fingers of the DNA-binding domain of WT1. Desmoplastic small round cell Tumor represents the third Tumor type associated with translocation of EWS and the first Tumor associated with consistent translocation of WT1. The chimeric products are predicted to modulate transcription at WT1 target sites and contribute to development of this unique Tumor.
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fusion of the ews and wt1 genes in the Desmoplastic small round cell Tumor
Cancer Research, 1994Co-Authors: Marc Ladanyi, William L GeraldAbstract:Abstract The Desmoplastic small round cell Tumor (DSRCT) is a recently recognized type of primitive sarcoma defined by a predilection for young males, aggressive clinical behavior, widespread abdominal serosal involvement, and a primitive histological appearance with prominent desmoplasia and striking divergent, multilineage differentiation. Previous cytogenetic case reports have identified a recurrent translocation, t(11;22) (p13;q12). We have characterized this translocation at the molecular level in a panel of five DSRCTs using a candidate gene approach. Southern blot analysis revealed recurrent rearrangement of both EWS, located at 22q12, and rearranged in other Tumor-specific translocations in Ewing9s sarcoma and clear cell sarcoma, and of WT1, the gene at 11p13 involved in a subset of Wilms9 Tumor. Consistent comigration of the rearranged EWS and WT1 bands in multiple enzyme digests indicated fusion of the genomic sequences, presumably due to the translocation t(11;22) (p13;q12). Northern blotting showed aberrant EWS and WT1 transcripts of the same size, suggesting the presence of a chimeric messenger RNA. This was confirmed by reverse transcriptase polymerase chain reaction using an EWS exon 7 primer and WT1 exon 8 or 9 primers, which revealed single polymerase chain reaction products consistent with a junction of EWS exon 7 to WT1 exon 8. DSRCT thus represents the third primitive sarcoma in which the EWS gene is involved and the first instance of recurrent rearrangement of a Tumor suppressor gene, WT1, in a specific Tumor type. The different translocation partners of the EWS gene, all of which are putative or definite transcription factor genes, may be responsible for the biological differences between DSRCT, Ewing9s sarcoma, and clear cell sarcoma.
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intra abdominal Desmoplastic small round cell Tumor report of 19 cases of a distinctive type of high grade polyphenotypic malignancy affecting young individuals
The American Journal of Surgical Pathology, 1991Co-Authors: William L Gerald, Hariatmi K Miller, Hector Battifora, Markku Miettinen, Elvio G Silva, Juan RosaiAbstract:Nineteen cases of a distinctive type of malignant small-cell Tumor are presented. The main features of the entity are as follows: a predilection for adolescent males (mean age: 18.6 years); predominant or exclusive intra-abdominal location, with only inconstant and secondary organ involvement; nesting pattern of growth; focal rhabdoid features; intense Desmoplastic reaction; immunohistochemical reactivity for epithelial [keratin, epithelial membrane antigen (EMA)], neural [neuron-specific enolase (NSE)], and muscle (desmin) markers; and highly aggressive behavior. It is proposed that this represents yet another member of the continuously enlarging and evolving family of small round (blue) cell Tumors of infancy and childhood that features, more than any other member of this group, the capacity for simultaneous multidirectional phenotypical expression.
Charles Honore - One of the best experts on this subject based on the ideXlab platform.
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can we cure patients with abdominal Desmoplastic small round cell Tumor results of a retrospective multicentric study on 100 patients
Surgical Oncology-oxford, 2019Co-Authors: Charles Honore, Jeanbaptiste Delhorme, E Nassif, M Faron, G Ferron, Emmanuelle Bompas, Olivier Glehen, Antoine Italiano, Francois Bertucci, Daniel OrbachAbstract:Abstract Background Despite being associated with a very poor prognosis, long-term survivors across all series of Desmoplastic Small Round Cell Tumor (DSRCT) have been reported. Aim of the study To analyze patients ‘characteristics associated with a prolonged survival after DSRCT diagnosis. Methods All consecutive patients treated for DSRCT in nine French expert centers between 1991 and 2018 were retrospectively analyzed. Patients with a follow-up of less than 2 years were excluded and cure defined as being disease-free at least 5 years. Results 100 pts were identified (median age 25 years, 89% male). 27 had distant metastases at diagnosis and 80 pts underwent upfront chemotherapy (CT). 71 pts were operated, 20 pts without prior CT). Surgery was macroscopically complete (CC0/1) in 50 pts. Hyperthermic intraperitoneal Chemotherapy (HIPEC) was administered during surgery in 15 pts 54 pts had postoperative CT and 26 pts had postoperative whole abdomino-pelvic RT (WAP-RT). After a median follow-up of 103 months (range 23–311), the median overall survival (OS) was 25 months. The 1- year, 3-year and 5-year OS rates were 90%, 35% and 4% respectively. 5 patients were considered cured after a median disease-free interval of 100 months (range 22–139). Predictive factors of cure were female sex (HR = 0.49, p = 0.014), median PCI Conclusion Cure in DSRCT is possible in 5% of patients and is best achieved combining systemic chemotherapy, complete cytoreductive surgery and WAP-RT. Despite aggressive treatment, recurrence is common and targeted therapies are urgently needed.
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abdominal Desmoplastic small round cell Tumor without extraperitoneal metastases is there a benefit for hipec after macroscopically complete cytoreductive surgery
PLOS ONE, 2017Co-Authors: Charles Honore, Jeanbaptiste Delhorme, G Ferron, Daniel Orbach, V Atallah, Olivier Mir, C Lepechoux, Pascale Philippechomette, Sabine Sarnacki, Simon MsikaAbstract:Background Desmoplastic Small Round Cell Tumor (DSRCT) is a rare disease affecting predominantly children and young adults and for which the benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) after complete cytoreductive surgery (CCRS) remains unknown. Methods To identify patients with DSRCT without extraperitoneal metastases (EPM) who underwent CCRS between 1991 and 2015, a retrospective nation-wide survey was conducted by crossing the prospective and retrospective databases of the French Network for Rare Peritoneal Malignancies, French Reference Network in Sarcoma Pathology, French Sarcoma Clinical Network and French Pediatric Cancer Society. Results Among the 107 patients with DSRCT, 48 had no EPM and underwent CCRS. The median peritoneal cancer index (PCI) was 9 (range: 2–27). Among these 48 patients, 38 (79%) had pre- and/or postoperative chemotherapy and 23 (48%) postoperative whole abdominopelvic radiotherapy (WAP-RT). Intraperitoneal chemotherapy was administered to 11 patients (23%): two received early postoperative intraperitoneal chemotherapy (EPIC) and nine HIPEC. After a median follow-up of 30 months, the median overall survival (OS) of the entire cohort was 42 months. The 2-y and 5-y OS were 72% and 19%. The 2-y and 5-y disease-free survival (DFS) were 30% and 12%. WAP-RT was the only variable associated with longer peritoneal recurrence-free survival and DFS after CCRS. The influence of HIPEC/EPIC on OS and DFS was not statistically conclusive. Conclusion The benefit of HIPEC is still unknown and should be evaluated in a prospective trial. The value of postoperative WAP-RT seems to be confirmed.
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abdominal Desmoplastic small round cell Tumor multimodal treatment combining chemotherapy surgery and radiotherapy is the best option
Annals of Surgical Oncology, 2015Co-Authors: Charles Honore, Koceila Amroun, Laurence Vilcot, Julien Domont, Philippe Terrier, Axel Le Cesne, Cecile Le Pechoux, Sylvie BonvalotAbstract:Background With nearly 450 cases reported since 1991, Desmoplastic small round cell Tumor (DSRCT) is a rare abdominal Tumor typically arising in adolescent and young adult white men. With no large series described, the best therapeutic strategy remains unclear.
Larry Argatoff - One of the best experts on this subject based on the ideXlab platform.
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detection of the ews wt1 gene fusion by reverse transcriptase polymerase chain reaction in the diagnosis of intra abdominal Desmoplastic small round cell Tumor
The American Journal of Surgical Pathology, 1996Co-Authors: Larry Argatoff, John X Oconnell, Joan Mathers, C B Gilks, Poul H SorensenAbstract:We report two cases of intra-abdominal Desmoplastic small round cell Tumor with characteristic clinical, histological, immunohistochemical, and ultrastructural features. Fusion of the EWS gene on chromosome 22 and the WT1 gene on chromosome 11, resulting from the chromosomal translocation t(11;22)(p13;q12), was detected by reverse transcriptase polymerase chain reaction (RT-PCR) in both cases. This translocation has been previously reported in this type of Tumor using either cytogenetic or molecular biological techniques. Tumor tissue from both cases revealed no chimeric fusion transcripts characteristic of the Ewing sarcoma family of peripheral primitive neuroectodermal Tumors or of alveolar rhabdomyosarcoma, two Tumors in the differential diagnosis of intra-abdominal Desmoplastic small round cell Tumor. This report demonstrates the utility of molecular studies as an adjunct in the diagnosis of this rare and aggressive Tumor.
Daniel Orbach - One of the best experts on this subject based on the ideXlab platform.
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can we cure patients with abdominal Desmoplastic small round cell Tumor results of a retrospective multicentric study on 100 patients
Surgical Oncology-oxford, 2019Co-Authors: Charles Honore, Jeanbaptiste Delhorme, E Nassif, M Faron, G Ferron, Emmanuelle Bompas, Olivier Glehen, Antoine Italiano, Francois Bertucci, Daniel OrbachAbstract:Abstract Background Despite being associated with a very poor prognosis, long-term survivors across all series of Desmoplastic Small Round Cell Tumor (DSRCT) have been reported. Aim of the study To analyze patients ‘characteristics associated with a prolonged survival after DSRCT diagnosis. Methods All consecutive patients treated for DSRCT in nine French expert centers between 1991 and 2018 were retrospectively analyzed. Patients with a follow-up of less than 2 years were excluded and cure defined as being disease-free at least 5 years. Results 100 pts were identified (median age 25 years, 89% male). 27 had distant metastases at diagnosis and 80 pts underwent upfront chemotherapy (CT). 71 pts were operated, 20 pts without prior CT). Surgery was macroscopically complete (CC0/1) in 50 pts. Hyperthermic intraperitoneal Chemotherapy (HIPEC) was administered during surgery in 15 pts 54 pts had postoperative CT and 26 pts had postoperative whole abdomino-pelvic RT (WAP-RT). After a median follow-up of 103 months (range 23–311), the median overall survival (OS) was 25 months. The 1- year, 3-year and 5-year OS rates were 90%, 35% and 4% respectively. 5 patients were considered cured after a median disease-free interval of 100 months (range 22–139). Predictive factors of cure were female sex (HR = 0.49, p = 0.014), median PCI Conclusion Cure in DSRCT is possible in 5% of patients and is best achieved combining systemic chemotherapy, complete cytoreductive surgery and WAP-RT. Despite aggressive treatment, recurrence is common and targeted therapies are urgently needed.
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abdominal Desmoplastic small round cell Tumor without extraperitoneal metastases is there a benefit for hipec after macroscopically complete cytoreductive surgery
PLOS ONE, 2017Co-Authors: Charles Honore, Jeanbaptiste Delhorme, G Ferron, Daniel Orbach, V Atallah, Olivier Mir, C Lepechoux, Pascale Philippechomette, Sabine Sarnacki, Simon MsikaAbstract:Background Desmoplastic Small Round Cell Tumor (DSRCT) is a rare disease affecting predominantly children and young adults and for which the benefit of hyperthermic intraperitoneal chemotherapy (HIPEC) after complete cytoreductive surgery (CCRS) remains unknown. Methods To identify patients with DSRCT without extraperitoneal metastases (EPM) who underwent CCRS between 1991 and 2015, a retrospective nation-wide survey was conducted by crossing the prospective and retrospective databases of the French Network for Rare Peritoneal Malignancies, French Reference Network in Sarcoma Pathology, French Sarcoma Clinical Network and French Pediatric Cancer Society. Results Among the 107 patients with DSRCT, 48 had no EPM and underwent CCRS. The median peritoneal cancer index (PCI) was 9 (range: 2–27). Among these 48 patients, 38 (79%) had pre- and/or postoperative chemotherapy and 23 (48%) postoperative whole abdominopelvic radiotherapy (WAP-RT). Intraperitoneal chemotherapy was administered to 11 patients (23%): two received early postoperative intraperitoneal chemotherapy (EPIC) and nine HIPEC. After a median follow-up of 30 months, the median overall survival (OS) of the entire cohort was 42 months. The 2-y and 5-y OS were 72% and 19%. The 2-y and 5-y disease-free survival (DFS) were 30% and 12%. WAP-RT was the only variable associated with longer peritoneal recurrence-free survival and DFS after CCRS. The influence of HIPEC/EPIC on OS and DFS was not statistically conclusive. Conclusion The benefit of HIPEC is still unknown and should be evaluated in a prospective trial. The value of postoperative WAP-RT seems to be confirmed.
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Desmoplastic small round cell Tumors with ews wt1 fusion transcript in children and young adults
Pediatric Blood & Cancer, 2012Co-Authors: Pascale Philippechomette, Jean-yves Blay, Nabil Kabbara, Nicolas Andre, Gaelle Pierron, Aurore Coulomb, Valerie Laurence, Olivier Delattre, Gudrun Schleiermacher, Daniel OrbachAbstract:Background The presence of the EWS-WT1 gene fusion transcript (GFT) is characteristic of Desmoplastic small round cell Tumor (DSRCT), a rare and very aggressive disease for which the treatment has not yet been clearly standardized. Methods This was a retrospective national multicenter analysis of young patients <30 years with Tumors expressing the EWS-WT1-GFT, designed to determine whether extensive surgery had an impact on survival. Results Between 1995 and 2006, a EWS-WT1-GFT was detected in the Tumors of 38 patients, 17 (44.7%) of whom had had a different initial pathologic diagnosis prior to molecular testing. Mean age was 13.2 years (range: 4–29.7 years). Only 9 patients (24%) had localized disease. Treatment was heterogeneous. Nine patients had “limited” surgical resections and 22 underwent “extensive” surgery. Two-year event-free survival and overall survival were 14.4% and 50%, respectively. Among the five patients who were alive in complete remission, four had undergone extensive and complete surgery. Conclusions Detection of the EWS-WT1-GFT plays a major role in the diagnosis of DSRCT. No survival difference was observed according to extent of surgery, but complete surgery seemed to offer the best chance of long-term survival. High-dose chemotherapy or local radiotherapy did not appear to improve survival in this retrospective analysis, but larger prospective studies are needed to provide definitive conclusions on the role of these treatments. Pediatr Blood Cancer 2012; 58: 891–897. © 2011 Wiley Periodicals, Inc.