scholarly journals Aberrations of TBX2-CHK2-p53 Signaling Pathway and its Role in Malignant Peripheral Nerve Sheath Tumors

2020 ◽  
pp. 1-10
Author(s):  
Jilong Yang ◽  
Chao Zhang ◽  
Fangyuan Chang ◽  
Hongji Dai ◽  
Jilong Yang ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Signaling Pathway ◽  
Nerve Sheath Tumor ◽  
Ki 67 ◽  
P53 Expression ◽  
Genetic Aberrations ◽  
Peripheral Nerve Sheath Tumors ◽  
P53 Signaling ◽  
Nerve Sheath ◽  
P53 Signaling Pathway

Background and Objectives: The dismal outcome of malignant peripheral nerve sheath tumor (MPNST) highlights the necessity of identifying new biomarkers and pathogenesis for this aggressive sarcoma. Therefore, it is necessary to detect the aberrations of the TBX2-CHK2-p53 pathway and investigate its biological role in MPNST. Methods: Genetic aberrations of TBX2, CHK2 and p53 were detected by next generation sequencing (NGS) in 10 MPNST samples. Protein expression of TBX2, CHK2, p53, Ki-67 and cyclin D1 were assessed by immunohistochemistry (IHC) in 63 MPNST samples. Results: Our present data demonstrated that there were gene mutations of TBX2, CHK2 and p53 in MPNST samples. TBX2 expression was correlated with American Joint Committee on Cancer (AJCC) stage, recurrence and metastasis. Correlation analysis found that TBX2 was positively correlated with CHK2 (p=0.045) and CHK2 was positively correlated with p53 (p=0.006). Furthermore, both CHK2 and p53 were positively correlated with Ki-67 (p<0.05), which is related to tumor differentiation, metastasis and prognosis. As for survival analyses, patients with high TBX2, CHK2 and p53 expression exhibited shorter disease-free survival (DFS) and overall survival (OS), respectively (p<0.05) and TBX2 and CHK2 were independent prognostic factors for MPNST patients (p<0.05). Conclusion: There are genetic aberrations of the TBX2-CHK2-p53 signaling pathway in MPNST, which might promote the progression of MPNST by increasing Ki-67 expression. Thus, TBX2 and CHK2 might be useful markers for MPNST.

scholarly journals Malignant peripheral nerve sheath tumor with and without neurofibromatosis type 1

2017 ◽  
Vol 75 (6) ◽  
pp. 366-371 ◽  
Author(s):  
Roberto André Torres de Vasconcelos ◽  
Pedro Guimarães Coscarelli ◽  
Regina Papais Alvarenga ◽  
Marcus André Acioly
Keyword(s):  
Overall Survival ◽  
Peripheral Nerve ◽  
Neurofibromatosis Type 1 ◽  
Tumor Size ◽  
Retrospective Chart Review ◽  
Neurofibromatosis Type ◽  
Nerve Sheath Tumor ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath

ABSTRACT Objective In this study, we review the institution’s experience in treating malignant peripheral nerve sheath tumors (MPNSTs). A secondary aim was to compare outcomes between MPNSTs with and without neurofibromatosis type 1 (NF1). Methods Ninety-two patients with MPNSTs, over a period of 20 years, were reviewed. A retrospective chart review was performed. The median age was 43.5 years (range, 3–84 years) and 55.4% were female; 41 patients (44.6%) had NF1-associated tumors. Results Mean tumor sizes were 15.8 ± 8.2 cm and 10.8 ± 6.3 cm for patients with and without NF1, respectively. Combined two- and five-year overall survival was 48.5% and 29%. Multivariate analysis confirmed the association of tumor size greater than 10 cm (hazard ratio (HR) 2.99; 95% confidence interval (CI) 1.14–7.85; p = 0.0258) and presence of NF1 (HR 3.41; 95%CI 1.88–6.19; p < 0.001) with a decreased overall survival. Conclusion Tumor size and NF1 status were the most important predictors of overall survival in our population.

FORAMINAL NERVE SHEATH TUMORS

Neurosurgery ◽  
2009 ◽  
Vol 64 (suppl_2) ◽  
pp. A33-A43 ◽  
Author(s):  
Judith A. Murovic ◽  
Iris C. Gibbs ◽  
Steven D. Chang ◽  
Bret C. Mobley ◽  
Jon Park ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Medical Center ◽  
Nerve Sheath Tumor ◽  
Peripheral Nerve Sheath Tumor ◽  
Central Necrosis ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Neurological Findings ◽  
Nerve Sheath ◽  
Asymptomatic Case

Abstract OBJECTIVE To conduct a retrospective review of outcomes in 15 patients with 18 foraminal tumors, including 17 benign peripheral nerve sheath tumors and 1 malignant peripheral nerve sheath tumor, who underwent CyberKnife (Accuray, Inc., Sunnyvale, CA) radiosurgery at Stanford University Medical Center from 1999 to 2006. METHODS Symptoms and findings, neurofibromatosis (NF) association, previous radiation, imaging, dosimetry, tumor volume, central necrosis, and the relation of these factors to outcomes were evaluated. RESULTS Before treatment, 1 asymptomatic patient had radiculopathic findings, 3 patients experienced local pain with intact neurological examinations, and 7 patients had radiculopathic complaints with intact (1 patient), radiculopathic (4 patients), or radiculomyelopathic examinations (2 patients). Five patients had myelopathic complaints and findings. Three patients had NF1-associated neurofibromas, 1 patient with NF2 had a schwannoma, and 1 patient had a schwannomatosis-related lesion. Two likely radiation-induced lesions, a neurofibroma and a malignant peripheral nerve sheath tumor, were observed. Prescribed doses ranging from 16 to 24 Gy, delivered in 1 to 3 fractions of 6 to 20 Gy, resulted in maximum tumor doses ranging from 20.9 to 30 Gy. Target volumes ranged from 1.36 to 16.9 mL. After radiosurgery, the asymptomatic case remained asymptomatic, and neurological findings improved. Thirteen of 15 symptomatic patients with (12 patients) or without (3 patients) neurological findings improved (3 cases after resection) or remained stable, and 2 patients worsened. Symptoms and examinations remained stable or improved in 8 (80%) of 10 patients with schwannomas and 3 (60%) of 5 patients with neurofibromas. Tumor volumes decreased in 12 (67%) of 18 tumors and increased in 3 tumors. Tumor volumes decreased in 8 of 10 schwannomas and 3 of 7 neurofibromas. Central necrosis developed in 8 (44%) of 18 tumors. CONCLUSION CyberKnife radiosurgery resulted in pain relief and functional preservation in selected foraminal peripheral nerve sheath tumors and a malignant peripheral nerve sheath tumor. Symptomatic and neurological improvements were more noticeable with schwannomas. Myelopathic symptoms may necessitate surgical debulking before radiosurgery.

Malignant Peripheral Nerve Sheath Tumor With Rhabdomyosarcomatous Differentiation (Malignant Triton Tumor)

2006 ◽  
Vol 130 (12) ◽  
pp. 1878-1881 ◽  
Author(s):  
Christopher J. Stasik ◽  
Ossama Tawfik
Keyword(s):  
Peripheral Nerve ◽  
Correct Diagnosis ◽  
Strong Association ◽  
Clinical History ◽  
Nerve Sheath Tumor ◽  
Malignant Triton Tumor ◽  
Peripheral Nerve Sheath Tumor ◽  
Prognostic Features ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath

Abstract Malignant peripheral nerve sheath tumors arise from Schwann cells or within existing neurofibromas and have a strong association with type 1 neurofibromatosis. These tumors are histologically diverse and may contain malignant areas of divergent mesenchymal differentiation, the most common of which is skeletal muscle (rhabdomyosarcoma). Malignant peripheral nerve sheath tumor with rhabdomyosarcomatous differentiation is also known as malignant triton tumor. Malignant triton tumor has a worse prognosis than classic malignant peripheral nerve sheath tumor does, and the correct diagnosis requires attention to the clinical history and knowledge of the complexities regarding its differential diagnosis. In this review we discuss the clinical, histopathological, immunohistochemical, and prognostic features of this rare neoplasm.

scholarly journals The Role of Polycomb Repressive Complex in Malignant Peripheral Nerve Sheath Tumor

Genes ◽  
2020 ◽  
Vol 11 (3) ◽  
pp. 287 ◽  
Author(s):  
Xiyuan Zhang ◽  
Béga Murray ◽  
George Mo ◽  
Jack F. Shern
Keyword(s):  
Peripheral Nerve ◽  
Transcriptional Repression ◽  
Molecular Mechanisms ◽  
Significant Proportion ◽  
Soft Tissue Sarcomas ◽  
Nerve Sheath Tumor ◽  
Polycomb Repressive Complex ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath ◽  
Recurrent Mutations

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive soft tissue sarcomas that can arise most frequently in patients with neurofibromatosis type 1 (NF1). Despite an increasing understanding of the molecular mechanisms that underlie these tumors, there remains limited therapeutic options for this aggressive disease. One potentially critical finding is that a significant proportion of MPNSTs exhibit recurrent mutations in the genes EED or SUZ12, which are key components of the polycomb repressive complex 2 (PRC2). Tumors harboring these genetic lesions lose the marker of transcriptional repression, trimethylation of lysine residue 27 on histone H3 (H3K27me3) and have dysregulated oncogenic signaling. Given the recurrence of PRC2 alterations, intensive research efforts are now underway with a focus on detailing the epigenetic and transcriptomic consequences of PRC2 loss as well as development of novel therapeutic strategies for targeting these lesions. In this review article, we will summarize the recent findings of PRC2 in MPNST tumorigenesis, including highlighting the functions of PRC2 in normal Schwann cell development and nerve injury repair, as well as provide commentary on the potential therapeutic vulnerabilities of a PRC2 deficient tumor cell.

scholarly journals Systemic Treatment for Advanced and Metastatic Malignant Peripheral Nerve Sheath Tumors—A Sarcoma Reference Center Experience

2020 ◽  
Vol 9 (10) ◽  
pp. 3157
Author(s):  
Paweł Sobczuk ◽  
Paweł Teterycz ◽  
Anna M. Czarnecka ◽  
Tomasz Świtaj ◽  
Hanna Koseła-Paterczyk ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Systemic Treatment ◽  
Treatment Options ◽  
Soft Tissue Sarcomas ◽  
Nerve Sheath Tumor ◽  
First Line ◽  
Rare Type ◽  
Reference Center ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath

Malignant peripheral nerve sheath tumor (MPNST) is a rare type of soft tissue sarcomas. The localized disease is usually treated with surgery along with perioperative chemo- or radiotherapy. However, up to 70% of patients can develop distant metastases. The study aimed to evaluate the modes and outcomes of systemic treatment of patients with diagnosed MPNST treated in a reference center. In total, 115 patients (56 female and 59 male) diagnosed with MPNST and treated due to unresectable or metastatic disease during 2000–2019 were included in the retrospective analysis. Schemes of systemic therapy and the outcomes—progression-free survival (PFS) and overall survival (OS)—were evaluated. The median PFS in the first line was 3.9 months (95% CI 2.5–5.4). Doxorubicin-based regimens were the most commonly used in the first line (50.4% of patients). There were no significant differences in PFS between chemotherapy regimens most commonly used in the first line (p = 0.111). The median OS was 15.0 months (95% CI 11.0–19.0) and the one-year OS rate was 63%. MPNST are resistant to the majority of systemic therapies, resulting in poor survival in advanced settings. Chemotherapy with doxorubicin and ifosfamide is associated with the best response and longest PFS. Future studies and the development of novel treatment options are necessary for the improvement of treatment outcomes.

scholarly journals Retrospective canine skin peripheral nerve sheath tumors data with emphasis on histologic, immunohistochemical and prognostic factors

2015 ◽  
Vol 35 (12) ◽  
pp. 965-974 ◽  
Author(s):  
Gisele S. Boos ◽  
Daniele M. Bassuino ◽  
Fabiana Wurster ◽  
Neusa B. Castro ◽  
Tatiane T.N. Watanabe ◽  
...  
Keyword(s):  
Peripheral Nerve ◽  
Protein S ◽  
Skin Neoplasms ◽  
Tumor Location ◽  
Benign Tumors ◽  
Nerve Sheath Tumor ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath ◽  
S 100

Abstract: In this retrospective study was determined the frequency of canine skin peripheral nerve sheath tumors (PNST) in cases diagnosed by the Setor de Patologia Veterinária of the Universidade Federal do Rio Grande do Sul (SPV-UFRGS), Brazil, between the years 2000 and 2012. The canine profiles, as well as histological, immunohistochemical and prognostic aspects of the tumors were based on 70 samples, comprising 40 females, 29 males and one unspecified sample. Between 2000 and 2012, 2,984 skin tumors of dogs were diagnosed in the SPV-UFRGS, totaling 2.34% of skin neoplasms in dogs. Animals that comprised the largest amount of samples (43%) were those with no breed (SRD), followed by German Shepherds (10%). Females were more affected than males (40/70 - 57% and 29/70 - 41% respectively). Skin PNST of this research showed predominant localization on the limbs (40% in the forelimbs and 29% in the hindlimbs); affecting adult dogs, mostly aged between 8 and 11 years (54%). The samples were routinely processed for hematoxylin and eosin, and were also evaluated by toluidine blue and Masson's trichrome staining, and immunohistochemistry (IHC) anti-vimentin, -S-100, -GFAP, -actin, von Willebrand factor and neurofilament. Anisocytosis and anisokaryosis, mitotic index, intratumoral necrosis, invasion of adjacent tissues, tumor location, local recurrence and metastasis were related to the diagnosis of benign (49/70) or malignant tumor (21/70). The Antoni A histological pattern was observed more frequently in benign tumors. The immunohistochemistry helped to diagnose PNST, and anti-vimentin and anti-protein S-100 showed the highest rates of immunostaining. Throughout statistical analysis of animals with tumor recurrence, it was found that the chance of an animal with a malignant peripheral nerve sheath tumor to develop recurrence is 4.61 times higher than in an animal that had a benign tumor.

Primary malignant peripheral nerve sheath tumor of the spine with acute hydrocephalus: a rare clinical entity

2014 ◽  
Vol 21 (3) ◽  
pp. 367-371 ◽  
Author(s):  
Yaxiong Li ◽  
Fengshi Fan ◽  
Jianguo Xu ◽  
Jie An ◽  
Weining Zhang
Keyword(s):  
Peripheral Nerve ◽  
English Language ◽  
Standard Of Care ◽  
Nerve Sheath Tumor ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath ◽  
History Of ◽  
Brain Ct Scan ◽  
The Right

Primary malignant peripheral nerve sheath tumors (MPNSTs) are extremely rare in patients without a history of neurofibromatosis; only 18 cases have been reported in the English-language literature to this point. The authors report their experience with 1 new case of a primary MPNST. A 33-year-old woman presented with low-back pain radiating to the right calf that progressed over 1 year. Magnetic resonance imaging of the spine revealed an intradural extramedullary lesion at the T12–L1 level. The patient was diagnosed with primary MPNST, underwent two surgical excisions and radiation therapy, and developed leptomeningeal metastases as well as brain metastases. The patient revisited the emergency room with sudden loss of consciousness. A brain CT scan displayed bilateral lateral ventricle enlargement, for which a ventriculoperitoneal shunt was inserted. These symptoms have not been described in any previous report. Primary spinal MPNST is an exceedingly rare entity, and the overall prognosis is very poor. To the authors' knowledge, no standard of care for primary spinal MPNSTs has yet been established. All 19 cases of primary spinal MPNSTs are reviewed, and the authors discuss their clinical, radiological, and therapeutic features and outcomes.

Nerve Sheath Tumors—Schwannomas and Neurofibromas

2018 ◽  
Author(s):  
Christian Heinen ◽  
Thomas Kretschmer
Keyword(s):  
Peripheral Nerve ◽  
Nerve Sheath Tumor ◽  
Surgical Strategies ◽  
Treatment Timing ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Tumor ◽  
Nerve Sheath ◽  
Contrast Enhanced

A benign peripheral nerve sheath tumor is illustrated in a case presentation of a painful mass in the medial thigh, with paresthesias radiating along the course of the saphenous nerve. The presenting features, appropriate workup, treatment timing, surgical strategies, follow-up, and results for nerve-associated masses are outlined. Specific imaging findings for peripheral nerve sheath tumors on contrast-enhanced MR imaging and the merits of high-resolution ultrasound are detailed. The typical features of a well-defined and noninvasive peripheral nerve tumor, the principles of exploration, and microsurgical enucleation technique are highlighted. Other nerve tumor entities that should be considered in the differential diagnosis, as well as their respective features, are discussed.

scholarly journals Somatic Mutations of lats2 Cause Peripheral Nerve Sheath Tumors in Zebrafish

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 972 ◽  
Author(s):  
Zachary J. Brandt ◽  
Paula N. North ◽  
Brian A. Link
Keyword(s):  
Peripheral Nerve ◽  
Somatic Mutations ◽  
Tumor Formation ◽  
Hippo Signaling ◽  
Nerve Sheath Tumor ◽  
Peripheral Nerve Sheath Tumor ◽  
Nerve Sheath Tumors ◽  
Peripheral Nerve Sheath Tumors ◽  
Nerve Sheath ◽  
Early Lethality

The cellular signaling pathways underlying peripheral nerve sheath tumor (PNST) formation are poorly understood. Hippo signaling has been recently implicated in the biology of various cancers, and is thought to function downstream of mutations in the known PNST driver, NF2. Utilizing CRISPR-Cas9 gene editing, we targeted the canonical Hippo signaling kinase Lats2. We show that, while germline deletion leads to early lethality, targeted somatic mutations of zebrafish lats2 leads to peripheral nerve sheath tumor formation. These peripheral nerve sheath tumors exhibit high levels of Hippo effectors Yap and Taz, suggesting that dysregulation of these transcriptional co-factors drives PNST formation in this model. These data indicate that somatic lats2 deletion in zebrafish can serve as a powerful experimental platform to probe the mechanisms of PNST formation and progression.

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