Neuroectodermal differentiation in Ewing's sarcoma family of tumors does not predict tumor behavior

Parham, David M.; Hijazi, Yasmine M.; Steinberg, Seth M.; Meyer, William H.; Horowitz, Marc E.; Tzen, Chin Yuan; Wexler, Leonard H.; Tsokos, Maria

doi:10.1016/s0046-8177(99)90244-7

Cited by 102 publications

(47 citation statements)

References 24 publications

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“…23 Our findings are in agreement with these clinical observations in which neural differentiation was not found to be associated with a major change in clinical outcome. 22 In summary, Notch signaling is active in Ewing sarcoma human tumors and cell lines. Its inhibition induces neural differentiation.…”

Section: Discussionmentioning

confidence: 98%

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Inhibition of Notch Signaling Induces Neural Differentiation in Ewing Sarcoma

Baliko

Bright

Poon

et al. 2007

The American Journal of Pathology

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Cells from Ewing sarcoma exhibit cellular features and express markers, suggesting that the tumor is of neuroectodermal origin. Because Notch signaling regulates the differentiation of neuroectodermal cells during development, we examined the role of Notch signaling in Ewing sarcomas. We found that Ewing sarcomas express Notch receptors, ligands, and the Notch target gene HES1. To determine the functional implications of Notch signaling, we expressed tetracycline-regulated constitutively active, dominant-negative (DN), or wild-type Notch-1 receptors in two Ewing sarcoma cell lines, or we treated the cell lines with a ␥-secretase inhibitor. Expression of the constitutively active Notch-1 reduced proliferation and expression of the DN Notch-1 reduced apoptosis in vitro. However, there was only a small difference in the volume of tumors that formed when the cell lines expressing these constructs were implanted in nude mice. Xenograft tumors derived from the cell lines expressing DN Notch-1 exhibited a neural phenotype. Treatment with a ␥-secretase inhibitor caused similar changes as expression of the DN construct. Notch signaling plays a role in cell differentiation, proliferation, and apoptosis in Ewing sarcoma, but its inhibition is only associated with a small change in tumor growth potential.

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Section: Discussionmentioning

confidence: 98%

“…21 There is variability in the degree to which Ewing tumors exhibit a neural phenotype. 22,23 Notch signaling could be a factor responsible for the regulation of the neural phenotype in Ewing tumors. Given the development of pharmacological agents that modulate Notch signaling, modulating this pathway has potential therapeutic implications.…”

mentioning

confidence: 99%

Inhibition of Notch Signaling Induces Neural Differentiation in Ewing Sarcoma

Baliko

Bright

Poon

et al. 2007

The American Journal of Pathology

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“…The overall 5-year survival rates for localized and metastatic tumours range from 65% to 74% and 25% to 45%, respectively. 5,6 Tumours arising from the paraspinal region and scapular areas respond better to treatment, while abdominal and pelvic PNETs respond poorly. 7 a c b Figure 1 Ultrasonography (a) and Doppler scan (b) of the left chin revealed a well-defined heterogeneous hypoechoic mass at masseter region.…”

Section: Discussionmentioning

confidence: 99%

Imaging findings in mandibular primitive neuroectodermal tumour: a report of a rare case and review of the literature

Yeh

Yeow²,

Chu³

et al. 2011

Dentomaxillofacial Radiology

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Primitive neuroectodermal tumours (PNETs) are aggressive undifferentiated tumours that occur mainly in the central nervous system (CNS). Reviewing the literature, only six cases of primary PNET of the mandible have been reported. These rare tumours are usually overlooked in clinical practice. An 18-year-old woman who presented with dental caries and left cheek swelling was initially diagnosed with facial cellulitis, but the swelling persisted despite adequate intravenous antibiotic therapy. Subsequent ultrasound and MR examinations revealed a tumour originating from the left mandibular ramus. The ultrasonography-guided percutaneous core needle biopsy confirmed the diagnosis of peripheral PNET. The radiographic features of mandibular PNETs are similar to those of PNETs in other regions, except for haemorrhage, necrosis and calcification. In addition, this is the first reported case with sonographic and MR images of this rare tumour, and the first case that was diagnosed based on the ultrasonography-guided percutaneous core needle biopsy. Using these image characteristics, mandibular PNETs can be diagnosed more accurately.

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“…For example, cytokeratin subsets, especially CK7 and 19, 3,9,14 bcl-2, 15 CD56, 9 calponin, 16 beta-catenin, 17 and matrix metalloproteinase-2 (MMP-2) 18 have been reported as potentially useful in synovial sarcoma; p75 nerve growth factor receptor (NGFR), 19 nestin, 20 CD57, 7,21,22 CD34, 22 PGP9.5, 23 and GFAP 21 in malignant peripheral nerve sheath tumor; Fli-1 in Ewing sarcoma; 6 and neuroectodermal markers such as chromoganin, synaptophysin, and PGP9.5 in primitive neuroectodermal tumor. [24][25][26][27] In order to further characterize the immunohistochemical profiles of synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma in a model that mimics small biopsy sampling, we evaluated a series of 73 tumors in tissue microarrays with a panel of 22 antibodies potentially useful in the differential diagnosis. We then analyzed the data with hierarchical cluster analysis, a mathematical technique employed for analyzing large data sets, most often used for gene arrays.…”

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confidence: 99%

Cluster analysis of immunohistochemical profiles in synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma

2006

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As a result of overlapping morphologic and immunohistochemical features, it can be difficult to distinguish synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma/primitive neuroectodermal tumor in core biopsies. To analyze and compare immunohistochemical profiles, we stained tissue microarrays of 23 synovial sarcomas, 23 malignant peripheral nerve sheath tumors, and 27 Ewing sarcomas with 22 antibodies potentially useful in the differential diagnosis, and analyzed the data with cluster analysis. Stain intensity was scored as none, weak, or strong. For CD99, tumors with membranous accentuation were independently categorized. Cluster analysis sorted five groups, with like tumors clustering together. Synovial sarcoma clustered into two groups: one cytokeratin and EMA positive (n ¼ 11), the other mostly cytokeratin negative, EMA positive, bcl-2 positive and mostly CD56 positive (n ¼ 9). Malignant peripheral nerve sheath tumor clustered into two groups: one S100 positive, with nestin and NGFR positivity in most (n ¼ 10), the other mostly S100 negative, and variably but mostly weakly positive for nestin and NGFR (n ¼ 11). Ewing sarcomas clustered into a single group driven by membranous CD99 staining. Thirteen cases failed to cluster (outliers), while three Ewing sarcomas clustered into groups of other tumor types. Paired antibodies for each tumor type determined by visual assessment of cluster analysis data and statistical calculations of specificity, sensitivity, and predictive values showed that EMA/CK7 for synovial sarcoma, nestin/S100 for malignant peripheral nerve sheath tumor, and membranous CD99/Fli-1 for Ewing sarcoma yielded high specificity and positive predictive values. Cluster analysis also highlighted aberrant staining reactions and diagnostic pitfalls in these tumors. Hierarchical cluster analysis is an effective method for analyzing high-volume immunohistochemical data.

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Neuroectodermal differentiation in Ewing's sarcoma family of tumors does not predict tumor behavior

Cited by 102 publications

References 24 publications

Inhibition of Notch Signaling Induces Neural Differentiation in Ewing Sarcoma

Inhibition of Notch Signaling Induces Neural Differentiation in Ewing Sarcoma

Imaging findings in mandibular primitive neuroectodermal tumour: a report of a rare case and review of the literature

Cluster analysis of immunohistochemical profiles in synovial sarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma

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