Histological Study of Chordoma Origin From Fetal Notochordal Cell Rests

Shen, Jun; Shi, Qin; Lü, Jian; Wang, Donglai; Zou, Tianming; Yang, Huilin; Zhu, Guoqing

doi:10.1097/brs.0000000000000010

Cited by 23 publications

(12 citation statements)

References 21 publications

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“…Although the positive rate of brachyury is high, the staining showed focal positivity and, in some regions, negativity. Shen et al 24 reported that brachyury staining was positive in chordoma but was negative in the BNCT component around chordomas and was negative in fetal notochordal cell rests (NCRs), which are histopathologically similar to BNCTs. This may indicate the presence of negative brachyury regions in BNCTs, which may be bound up with the NCRs.…”

Section: Discussionmentioning

confidence: 99%

Benign notochordal cell tumour: clinicopathology and molecular profiling of 13 cases

Cui

et al. 2018

J Clin Pathol

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AimsTo study the clinicopathological and molecular features of benign notochordal cell tumours (BNCTs) and their differential diagnosis from chordoma.Methods13 cases of BNCT were investigated. The genome-wide copy number imbalances were performed using Oncoscan CNV array in three cases and fluorescence in situ hybridisation (FISH) detection of epidermal growth factor receptor (EGFR)/chromosome 7 enumeration probe (CEP7), LSI1p36/1q21, LSI19p13/19q13, CEP3/CEP12 and Telvysion 6 P was performed in 13 cases.ResultsAll 13 BNCTs were symptomatic and eight cases showed a close relationship with the bones of the skull base. The important histological character for differential diagnosis with chordoma was the absence of extracellular matrix and eosinophil cells and the presence of vacuoles in most tumour cells. Immunohistochemical staining of AE1/AE3, vimentin, epithelial membrane antigen, S-100 and brachyury (100% each) were positive in BNCTs. Gain of chromosome 7 occurred in 10 cases (76.9%), gain of 1p in four (30.8%), gain of 1q in five (38.5%), gain of 19p and 19q in five (38.5%), gain of chromosome 12 in 11 cases (84.6%), gain of 6p in eight (61.5%) and gain of chromosome 3 in four cases (30.8%).ConclusionsIn contrast to chordoma, chromosome gain or normal copy number was more common while chromosome loss was infrequent in BNCTs. This may be a differential diagnosis clue for chordoma and may be an important characteristic in the progression of notochordal cell tumours.

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Section: Discussionmentioning

confidence: 99%

Benign notochordal cell tumour: clinicopathology and molecular profiling of 13 cases

Cui

et al. 2018

J Clin Pathol

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“…Previous work has shown a heterogeneous population of chordoma tumor cells containing cells growing as a monolayer and within clusters, identified both by transmission electron microscopy and by bright field microscopy [28] . The chordoma cells express α6 integrin (CD49f), one of the laminin-binding integrins and a stem cell marker in many epithelial types, including nucleus pulposus stem cells of the primitive notochord from which chordomas are derived [3] , [6] . The 2D chordoma cells growing in a single cell monolayer expressed an extensive cytokeratin 8 and 18 filamentous network and F-actin ( Figure 1 A ).…”

Section: Resultsmentioning

confidence: 99%

“…However, while chordomas are slow growing and radioresistant, they are locally aggressive, invasive, and highly recurrent and present a clinical progression representative of malignant tumors. Chordomas arise from undifferentiated remnants of the primitive notochord [1] , [3] and surprisingly express epithelial-type characteristics [4] and a low growth fraction, indicative of slow-growing disease. Chordomas impinge on critical nerve functions present within the clival, vertebral, and sacral regions of the spine [5] and can locally invade surrounding laminin-rich muscle.…”

Section: Introductionmentioning

confidence: 99%

Targeting the Cohesive Cluster Phenotype in Chordoma via β1 Integrin Increases Ionizing Radiation Efficacy

et al. 2017

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Chordoma is a rare, radiation-resistant, skull-base and spinal tumor with high local recurrence containing mixed cell-adhesion phenotypes. We characterized DNA damage response (DDR) signaling (γH2AX, pKAP1, pATM) and survival response to ionizing radiation (IR) in human chordoma samples (42 resections, 23 patients) to test if blocking cell adhesion sensitizes U-CH1 tumor cells to IR. U-CH1 cells expressed brachyury, YAP, and laminin adhesion receptors (CD49c, CD49f, CD44), and approximately 15% to 20% of U-CH1 cells featured an α6 integrin-dependent (CD49f) cohesive cluster phenotype, which confers therapeutic resistance and aids metastasis. DDR to IR in U-CH1 cells was compared to normal prostate epithelial (PrEC) and tumor cells (DU145). Flow cytometry showed a dose- and time-dependent increase in γH2AX and pKAP1 expression in all cell lines. However, nearly 50% of U-CH1 cells exhibited nonresponsive phenotype to IR (measured by γH2AX and pKAP1) independent of cell cycle status. Immunofluorescence microscopy verified that only 15% of U-CH1 clustered cells were γH2AX or pKAP1 positive (versus 80% of nonclustered cells) 2 hours following 2-Gy IR. Conversely, both tumor cell lines were uniformly defective in pATM response. HYD1, a synthetic ECM ligand, inhibited DDR through an unresolved γH2AX response. β1 integrin-blocking antibody (AIIB2) decreased cell survival 50% itself and approximately doubled the IR-induced cell kill at all IR doses observed at 2 and 4 weeks posttreatment. These results suggest that a heterogeneity of DDR to IR exists within a chordoma population. Blocking integrin function alone and/or as an adjuvant to IR may eradicate chordomas containing the cohesive cluster phenotype.

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“…[5] In very few cases there are remnants of the notochord retained within intervertebral discs. [6] These remnants are termed notochord cell rests (NCRs). A chordoma is a cancer that arises from these NCRs.…”

Section: Introductionmentioning

confidence: 99%

Proton beam therapy in the management of skull base chordomas: systematic review of indications, outcomes, and implications for neurosurgeons

Matloob

Nasir

Choi

2016

British Journal of Neurosurgery

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Histological Study of Chordoma Origin From Fetal Notochordal Cell Rests

Abstract: Our study results supported histological similarity and homology of NCRs coexisting in chordoma and in fetal nucleus pulposus. Brachyury activation probably takes an important role in chordoma tumoregenesis.

Cited by 23 publications

References 21 publications

Benign notochordal cell tumour: clinicopathology and molecular profiling of 13 cases

Benign notochordal cell tumour: clinicopathology and molecular profiling of 13 cases

Targeting the Cohesive Cluster Phenotype in Chordoma via β1 Integrin Increases Ionizing Radiation Efficacy

Proton beam therapy in the management of skull base chordomas: systematic review of indications, outcomes, and implications for neurosurgeons

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