Expression of vascular endothelial growth factor receptor 2 (VEGFR-2), inducible nitric oxide synthase (iNOS), and Ki-M1P in skull base chordoma: a series of 145 tumors

Akhavan‐Sigari, Reza; Gaab, M. R.; Rohde, Veit; Brandis, Almuth; Tezval, Hossein; Abili, Mehdi; Eckardstein, Kajetan von; Ostertag, Helmut

doi:10.1007/s10143-013-0495-5

Cited by 24 publications

(14 citation statements)

References 28 publications

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“…According to the literature, VEGF has been shown to be expressed in 77.8% of 28 sacral chordomas 17 , 18 . Akhavan-Sigari et al 2013 19 reported low expression of VEGFR-2 in 145 clivus chordomas, yet high expression of VEGFR-2 was correlated with a poor prognosis in their samples. In addition, a recent report has described a durable stabilization of chordomas of the skull base and the sacrum, respectively, after treatment with Erlotinib, an EGFR antagonist given in combination with the antiangiogenetic agent Bevacizumab 20 .…”

Section: Discussionmentioning

confidence: 95%

Mutation Analysis of Nine Chordoma Specimens by Targeted Next-Generation Cancer Panel Sequencing

Fischer¹,

Scheipl²,

Zopf³

et al. 2015

J. Cancer

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Background: Chordoma is a rare primary malignant bone tumour. Treatment options are mainly restricted to surgical excision, since chordomas are largely resistant to conventional ionising radiation and chemotherapy. Thus, there is a strong need to gain more thorough insights into the molecular biology and genetics of chordoma to allow for the development of new therapeutic options. We performed an ultra-deep sequencing analysis to find novel mutations in cancer associated genes in chordomas to date unseen with Sanger sequencing.Material and Methods: Nine chordomas (skull base (n=3), mobile spine (n=4), and sacrum/coccyx (n=2) were screened for mutations in 48 cancer genes using the Hot Spot Cancer Panel (Illumina). All putative mutations were compared against multiple databases (e.g. NCBI, COSMIC, PolyPhen, EGB, SIFT) and published Copy Number Variation (CNV) data for chordoma.Results: Our results showed mutations with a frequency above 5% in tumorsuppressor- and onco-genes, revealing new possible driver genes for chordomas. We detected three different variants accounting for 11 point mutations in three cancer associated genes (KIT, KDR and TP53). None of the detected mutations was found in all samples investigated. However, all genes affected interact or are connected in pathway analysis. There were no correlations to already reported CNVs in the samples analysed.Conclusions: We identified mutations in the associated genes KIT, KDR, and TP53. These mutations have been described previously and have been predicted to be tolerated. Further results on a larger series are warranted. The driver mechanisms of chordoma still have to be identified.

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Section: Discussionmentioning

confidence: 95%

Mutation Analysis of Nine Chordoma Specimens by Targeted Next-Generation Cancer Panel Sequencing

Fischer¹,

Scheipl²,

Zopf³

et al. 2015

J. Cancer

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“…Chordomas, however, remain an elusive disease for which little has been translated into clinical applications. 4 Factors that have been associated with a potentially worse prognosis in chordoma include expression of pAKT, 10 Raf-1, 28 Survivin, 8 iNOS, 2,3 Ki-M1p, 3 VEG-FR-2, 3 and mTOR, 9 as well as overexpression of CDK4, 27 brachyury, 15 PDGFR-a, 1 EGFR, 1 c-MET, 1 SPHK1, 28 and p53. 27 Furthermore, epigenetic dysregulation with miR-1 11 or miR-1237-3p downregulation, 29 or overexpression of miR-140-3p 30 or miR-155 23 has been associated with a potentially worse prognosis.…”

Section: Discussionmentioning

confidence: 99%

Prospective validation of a molecular prognostication panel for clival chordoma

Zenonos

Fernández-Miranda

Mukherjee

et al. 2019

Journal of Neurosurgery

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OBJECTIVE There are currently no reliable means to predict the wide variability in behavior of clival chordoma so as to guide clinical decision-making and patient education. Furthermore, there is no method of predicting a tumor's response to radiation therapy. METHODS A molecular prognostication panel, consisting of fluorescence in situ hybridization (FISH) of the chromosomal loci 1p36 and 9p21, as well as immunohistochemistry for Ki-67, was prospectively evaluated in 105 clival chordoma samples from November 2007 to April 2016. The results were correlated with overall progression-free survival after surgery (PFSS), as well as progression-free survival after radiotherapy (PFSR). RESULTS Although Ki-67 and the percentages of tumor cells with 1q25 hyperploidy, 1p36 deletions, and homozygous 9p21 deletions were all found to be predictive of PFSS and PFSR in univariate analyses, only 1p36 deletions and homozygous 9p21 deletions were shown to be independently predictive in a multivariate analysis. Using a prognostication calculator formulated by a separate multivariate Cox model, two 1p36 deletion strata (0%-15% and > 15% deleted tumor cells) and three 9p21 homozygous deletion strata (0%-3%, 4%-24%, and ≥ 25% deleted tumor cells) accounted for a range of cumulative hazard ratios of 1 to 56.1 for PFSS and 1 to 75.6 for PFSR. CONCLUSIONS Homozygous 9p21 deletions and 1p36 deletions are independent prognostic factors in clival chordoma and can account for a wide spectrum of overall PFSS and PFSR. This panel can be used to guide management after resection of clival chordomas.

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“…Traditionally, chordomas and chondrosarcomas are not sensitive to chemotherapy [105,106] and there are no drugs approved for their treatment [106][107][108]. Dysregulation of different signaling pathways has been found in the development of chordomas and chondrosarcomas [109][110][111][112][113][114][115][116][117][118][119]. Agents that interrupt these signaling pathways could become attractive targets for anticancer therapy.…”

Section: Chemotherapymentioning

confidence: 99%

Skull Base Chordomas and Chondrosarcomas

et al. 2020

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Skull base chordomas account for less than 0.2% and chondrosarcomas for less than 0.15% of all intracranial tumors. Although their clinical and imaging presentations are similar, they derive from different origins. Chordomas arise from embryonic remnants of the primitive notochord and chondrosarcomas from primitive mesenchymal cells or from the embryonic rest of the cranial cartilaginous matrix. Both entities are characterized by infiltration and destruction of the surrounding bone and soft tissue and a high locoregional recurrence rate. Chondrosarcomas, when treated with similar complex strategies, display a much better prognosis than chordomas. The overall survival is approximately 65% for chordomas and 80% for chondrosarcomas at 5 years and 30 and 50%, respectively, at 10 years. Chordomas are divided into the following 3 histological types: classical (conventional), chondroid, and dedifferentiated. Chondrosarcomas have conventional, mesenchymal, clear cell, and dedifferentiated subgroups. Both tumor entities often present with nonspe-cific symptoms, and headaches are the most reported initial symptom. Computed tomography and magnetic resonance imaging are required to determine the tumor localization and the extent of tumor growth. The treatment philosophy is to maximize tumor resection, minimize morbidity, and preserve function. Neurosurgical approaches commonly used for the resection of intracranial chordomas and chondrosarcomas are transsphenoidal, transbasal, cranio-orbitozygomatic, transzygomatic extended middle fossa, transcondylar, and transmaxillary approaches. Chordomas and chondrosarcomas are not sensitive to chemotherapy and there are no approved drugs for their treatment. The present treatment concept is a combination of surgical resection with a maximal excision and preserving patients' quality of life by adjuvant radiotherapy for both chordomas and chondrosarcomas.

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Expression of vascular endothelial growth factor receptor 2 (VEGFR-2), inducible nitric oxide synthase (iNOS), and Ki-M1P in skull base chordoma: a series of 145 tumors

Cited by 24 publications

References 28 publications

Mutation Analysis of Nine Chordoma Specimens by Targeted Next-Generation Cancer Panel Sequencing

Mutation Analysis of Nine Chordoma Specimens by Targeted Next-Generation Cancer Panel Sequencing

Prospective validation of a molecular prognostication panel for clival chordoma

Skull Base Chordomas and Chondrosarcomas

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