Prognostic significance of immunohistochemical expression of VEGFR2 and iNOS in spinal chordoma

Akhavan‐Sigari, Reza; Gaab, M. R.; Rohde, Veit; Abili, Mehdi; Ostertag, Helmut

doi:10.1007/s00586-014-3417-5

Cited by 19 publications

(10 citation statements)

References 31 publications

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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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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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“…However, chordomas still present a great challenge to clinicians. [25] Factors associated with a potentially worse prognosis for patients with chordoma include pAKT, [26] Raf-1, [27] Survivin, [28] iNOS, [29,30] VEGFR-2, [30] and mTOR, [26] as well as overexpression of PDGFR-a, [31] brachyury, [32] CDK4, [27] c-MET, [31] and p53. [27] In addition, epigenetic dysregulation with miR111 or miR-1237-3p downregulation, [33] or overexpression of miR-140-3p [34] or miR-155 [35] may also be associated with poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

The clinical outcomes for chordomas in the cranial base and spine

Zhou¹,

Wu³

et al. 2019

Medicine

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Owing to the special growth pattern of chordomas and the limited treatment options currently available, the treatment of chordoma still remains difficult. In this study, we hope to further clarify the relationship between surgical treatment and radiotherapy of chordoma and disease progression. All patients with a primary histopathological diagnosis of clival or spinal chordomas recorded in our institution between 1976 and 2017 were examined. A total of 60 patients (location: skull base/clival, n = 24; vertebral column, n = 5; sacrum, n = 31) had a mean follow-up time of 7.7 years (range 12 months–35 years). Compared with patients who received subtotal resection (n = 5, 5-year and 10-year survival = 61% and 39%, respectively), the annual survival rate of patients who received total resection (n = 55, 5-year and 10-year survival = 67%, respectively) was significantly higher. The overall 10-year survival rate (58%) of patients treated with surgery alone was significantly different from those treated with a combination of surgery and radiation (73%). The long-term prognosis of sacral chordoma was the worst (10-year survival rate = 48%). The best treatment strategy for improved long-term survival in chordoma was a combination of surgical resection and radiation therapy. Adjuvant radiotherapy for chordoma significantly improves disease-free survival, although the long-term survival benefit remains to be determined. A worse prognosis and poor long-term survival are seen in sacral chordomas.

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“…In CRC epithelial tumor cells and tumor cells of urothelial carcinomas, high VEGFR-2 expression has been described as a good prognostic factor [ 18 , 30 , 31 ]. Contrastingly, in tumor cells of chordomas [ 32 ], squamous cell carcinomas of the lung [ 33 ], hepatocarcinomas [ 34 ], high-grade gliomas [ 35 ] and DLBCL [ 23 ], high VEGFR-2 expression has been described as a poor prognostic factor.…”

Section: Discussionmentioning

confidence: 99%

The Prognostic Value of the Combination of Low VEGFR-1 and High VEGFR-2 Expression in Endothelial Cells of Colorectal Cancer

D’Haene

Koopmansch

Eycke

et al. 2018

IJMS

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Research on tumor angiogenesis has mainly focused on the vascular endothelial growth factor (VEGF) family and on methods to block its actions. However, reports on VEGF receptor (VEGFR) expression in tumor-associated endothelial cells (ECs) are limited. Thus, we evaluated VEGF, VEGFR-1 and VEGFR-2 expression in ECs of colorectal cancer (CRC) using immunohistochemistry. VEGF, VEGFR-1 and -2 expression in ECs was quantitatively evaluated by digital image analysis in a retrospective series of 204 tumor tissue samples and related to clinical variables. The data show that the VEGF, VEGFR-1 and VEGFR-2 expression in ECs is heterogeneous. Multivariate analysis including a set of clinicopathological variables reveals that high EC VEGFR-1 expression is an independent prognostic factor for overall survival (OS). The combination of low VEGFR-1 and high VEGFR-2 expression in ECs outperforms models integrating VEGFR-1 and VEGFR-2 as separate markers. Indeed, this VEGFR-1_VEGFR-2 combination is an independent negative prognostic factor for OS (p = 0.012) and metastasis-free survival (p = 0.007). In conclusion, this work illustrates the importance of studying the distribution of VEGF members in ECs of CRC. Interestingly, our preliminary data suggest that high VEGFR-1 and low VEGFR-2 expression in ECs appear to be involved in the progression of CRC, suggesting that targeting EC VEGFR-1 could offer novel opportunities for CRC treatment. However, a prospective validation study is needed.

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Prognostic significance of immunohistochemical expression of VEGFR2 and iNOS in spinal chordoma

Abstract: The high expression of VEGFR-2 and iNOS affected the OS. The OS at 10 years was only 30 %.

Cited by 19 publications

References 31 publications

Prospective validation of a molecular prognostication panel for clival chordoma

Prospective validation of a molecular prognostication panel for clival chordoma

The clinical outcomes for chordomas in the cranial base and spine

The Prognostic Value of the Combination of Low VEGFR-1 and High VEGFR-2 Expression in Endothelial Cells of Colorectal Cancer

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